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Biomedical subjects

J Jackson

Publications and source records attributed to J Jackson.

At least 199 records · Page 11Linked to original sources

Philadelphia chromosome positive childhood acute lymphoblastic leukemia: clinical and cytogenetic characteristics and treatment outcome. A Pediatric Oncology Group study.

Among 3,638 children with acute lymphoblastic leukemia (ALL) entered on Pediatric Oncology Group (POG) protocols between June 1981 and April 1989, successful cytogenetic studies were available for 2,519, 58 (2.3%) of which had the Philadelphia (Ph) chromosome detected. Features associated with the presence of the Ph chromosome were high leukocyte count (median, 33 x 10(9)/L), older age median, 9.6 years), a higher proportion of French-American-British L2 morphology, and a lower frequency of mediastinal mass. Immunologic marker studies at diagnosis in 56 Ph+ cases identified early pre-B ALL in 42 cases (75%), pre-B-cell in 9 (16%), and T-cell in 5 (9%). This distribution is similar to that found in Ph+ ALL. Intensive multiagent chemotherapy induced complete remissions in only 78% of eligible Ph+ patients compared with 96% of those without an identified Ph chromosome (P less than .001). Of 44 eligible Ph+ patients treated on POG frontline protocols for children with non-T, non-B-cell ALL, 27 have failed therapy, compared with 520 of 1,892 without an identified Ph chromosome (logrank P less than .001). Ph+ ALL is an aggressive form of acute leukemia that frequently presents in older children with a high leukocyte count, FAB L2 morphology, and a pseudodiploid karyotype, and becomes multidrug-resistant early. Thus, Ph+ cases require early identification to permit treatment with intensive induction regimens and experimental approaches such as bone marrow transplantation.

Asparaginase↗

Recurrent disseminated intravascular coagulation and fulminant intra hepatic thrombosis in a patient with the anti-phospholipid syndrome.

We describe a patient with the lupus anti-coagulant who had recurrent episodes, over a 2 year period, of a severe and disseminated intravascular coagulopathy. This patient also had positive serological assays for syphilis and anti-cardiolipin antibodies. Associated with the coagulopathy were co-expressed episodes of liver disease, ultimately terminating in fulminant liver failure. At autopsy the features were characteristic of the Budd-Chiari syndrome. This is the first report to document how consumptive coagulopathy may present as a dominant feature of the anti-phospholipid syndrome. It also clearly describes an immune mediated thrombotic mechanism as a cause of hepatic veno-occlusive disorders. Furthermore, this case highlights the varied clinical spectrum of the anti-phospholipid syndrome and suggests that a high index of suspicion is required to ensure its diagnosis.

Adult↗

Comparison of Coloscreen Self-Test and Haemoccult faecal occult blood tests in the detection of colorectal cancer in symptomatic patients.

The usefulness of faecal occult blood tests is limited by their acceptability to patients. Standard tests require the collection of a stool sample which may inhibit compliance. Self-read tests which avoid this step have therefore been devised. Coloscreen Self-Test (CST) and Haemoccult, which may be regarded as the standard slide test, were offered to 450 consecutive patients attending surgical outpatient clinics with symptoms suggestive of lower gastrointestinal disease. Both tests were successfully completed by 383 patients. Although 262 (68 per cent) patients indicated that they preferred CST this was not reflected in the overall compliance to the two tests (CST 86 per cent, Haemoccult 90 per cent). CST gave a positive result in only eight out of 24 patients with a colorectal cancer (sensitivity = 33 per cent) compared with 13 out of 24 for Haemoccult (sensitivity = 54 per cent). CST had no advantage from increased compliance to outweigh its lower sensitivity.

Colorectal Neoplasms↗

Ca2+ binding by Myxicola neurofilament proteins.

Titrimetric, 45Ca dialysis, and autoradiographic methods were used to examine how axoplasmic proteins from the giant neuron of the marine annelid Myxicola infundibulum bind calcium. Following the autoradiographic method of Maruyama et al., the 150-160 kD neurofilament subunits were identified as prominent intracellular Ca-binding peptides. Using equilibrium dialysis, extracts of axoplasmic proteins (greater than 50% neurofilament subunits) were examined in 300 mM KCl at different concentrations of free Ca and Mg, and at different pH. Axoplasmic proteins showed a high affinity Ca binding site (K1/2 3-6 microM, capacity 3-7 mumole g-1 protein) at pH 6.8 or pH 7.5. Changing the Mg concentration from 0 to 5 mM had no effect on the Ca binding. Elevating the dialysis pH from 7.0 to 9.0 reduced the apparent number of binding sites for Ca. Using microelectrodes to record the free Ca, microtitrations of axoplasmic proteins were completed by adding small amounts of CaCl2 to 100 microliters volumes of protein solutions. In a medium containing ionic constituents closely resembling those of the Myxicola axon, a Ca binding capacity of 5.0 mumole g-1 protein and a K1/2 of approximately 1 microM were measured.

Animals↗

Parents' accuracy in estimating child weight status.

Mothers of 107 preschool children estimated their child's weight status, and the accuracy of these estimates was examined. The majority of mothers (72%) were accurate. Of those who were inaccurate, 83% had underestimated the child's weight status, whereas only 17% had overestimated. Mothers of heavier children were more likely to underestimate their child's weight status.

Adult↗

Decision making of satisfied and dissatisfied married couples.

Ten satisfied and ten dissatisfied married couples described how they make decisions of low, moderate, and high levels of difficulty. Responses were coded as reflecting the use of equity, need-based, situational, or other norms. Results were consistent with previous findings that a state of equity is associated with marital satisfaction but also indicated that multiple norms are used in decision making of both satisfied and dissatisfied couples. Decision difficulty influenced use of both situational and need-based norms. A trend was found for satisfied husbands but not wives, to make greater use of need-based norms than dissatisfied husbands when decisions were high in difficulty. The results are interpreted as supporting a distinction between equity as a state and equity as a process and as supporting an instrumental value theory of norm use.

Adaptation, Psychological↗

Growth stimulation by coexpression of transforming growth factor-alpha and epidermal growth factor-receptor in normal and adenomatous human colon epithelium.

Autocrine stimulation of the epidermal growth factor receptor (EGF-R), by coexpression of transforming growth factor-alpha (TGF-alpha), causes malignant transformation of some fibroblast cell lines. TGF-alpha and EGF-R are both known to be expressed in colon carcinoma tissue and have been shown coexpressed in colon carcinoma cell lines. TGF-alpha autocrine activation of EGF-R has been suggested as a potential mechanism contributing to abnormal growth control in colon cancer. We now report coexpression of TGF-alpha and EGF-R transcripts in morphologically normal colonic epithelium from five individuals, in colonic adenomas from three individuals, and in a nontumorigenic colon adenoma cell line, VACO-330. Functional studies demonstrate VACO-330 growth is stimulated by exogenous TGF-alpha and is completely abolished by a blocking anti-EGF-R antibody. Autocrine stimulation of EGF-R by TGF-alpha is therefore required for growth of the adenoma cell line. Autocrine stimulation of EGF-R by TGF-alpha does not cause malignant transformation of the colonic epithelial cell. In normal and adenomatous human colon TGF-alpha, via either an autocrine or paracrine mechanism, is likely an important physiologic stimulant of epithelial proliferation.

Adenoma↗

Religious influence on menstrual attitudes and symptoms.

Menstrual attitudes and symptoms of 18 Orthodox Jewish Mikvah attenders, 23 Orthodox Jewish Mikvah non-attenders, 35 Protestant women, and 45 Catholic women were compared. When age, education, number of pregnancies, and religiosity were controlled, Mikvah non-attenders and Protestants most strongly endorsed a view of menstruation as a bothersome event. No significant differences were found, however, in expected or retrospectively reported menstrual symptoms. Correlational analyses indicated that attitudes, expectancies, and symptoms were significantly correlated only for the Catholic women. Differences between groups in religiosity and socialization were found. The Jewish women endorsed doctrines such as "menstruation makes women unclean" more than Catholic or Protestant women. Results support the hypothesized differential religious training regarding menstruation, but only offer weak support for the effects of this training on menstrual attitudes, expectancies, and symptoms.

Adult↗

Autoimmune angioedema: a new role for autoantibody in disease pathogenesis.

Angioedema may be due to hereditary forms of Cl-Inh deficiency, but recently an autoimmune form of angioedema has been described in which the mechanism is novel. While the peripheral blood monocytes of patients with autoimmune angioedema produce a normal, functionally active, 105 KD Cl-Inh in normal quantities, the Cl-Inh isolated from the patient's plasma exists in a dysfunctional lower molecular weight (96 KD) performance. Rather than bind and biologically inactivate the enzyme, a relatively common phenomenon in autoimmune disease, the autoimmune angioedema cleave the Cl-Inh molecule. The following sequence of events is proposed: structural and functionally normal Cl-Inh is synthesised and secreted, this secreted inhibitor is complexed by autoantibody and following enzyme interaction, denatured 96 KD Cl-Inh is proposed. This process depletes the pool of normal, functional Cl-Inh to critical levels and predisposes patients to episodes of oedema.

Angioedema↗

Six amino acids from the retroviral gene gag greatly enhance the transforming potential of the oncogene v-erb-B.

Avian erythroblastosis virus (AEV) induces both erythroblastosis and fibrosarcomas in susceptible birds and transforms the corresponding cells in culture. Neoplastic transformation by AEV is mediated principally by an oncogene known as v-erb-B. We have explored the means by which this gene is expressed from the genome of AEV and uncovered an important structural determinant for the potency of the oncogene. In order to define the boundaries of v-erb-B and the supplementary oncogene, v-erb-A, we sequenced all but a small portion of the genome of the ES4 strain of AEV. We then demonstrated that, during expression in infected cells, splicing fuses the first six amino acids of the retroviral gene gag to the body of the v-erb-B protein. In order to explore the impact of this fusion on the function of v-erb-B, we constructed vectors with Murine Leukemia Virus that express the oncogene either with or without the fusion to gag. Viruses generated from these two vectors differed greatly in their abilities to transform cells: fusion of v-erb-B with gag enhanced its transforming ability 50 to 100-fold as determined by focus transformation assays and growth in soft agar. Our data suggest that the difference in transforming ability is not due to alterations in transcription or translation but, rather, may result from changes in post-translational modification.

Amino Acid Sequence↗

Mixed connective tissue disease with arterial thrombosis, antiphospholipid antibodies and heparin induced thrombocytopenia.

We report a patient with mixed connective tissue disease (MCTD) who presented with thrombosis of the right femoral artery in association with antiphospholipid antibodies (aPL). When treated surgically and with heparin prophylaxis, she developed heparin induced thrombocytopenia and thrombosis which necessitated amputation of a lower limb. Thus our patient developed 2 separate groups of autoantibodies associated with thrombotic events. Our case highlights an association between thrombosis, aPL and MCTD. Furthermore, it emphasizes a need for intensive monitoring when hypercoaguable individuals with connective tissue disorders are treated with heparin.

Adult↗

IL-1 induces rapid phosphorylation of the IL-1 receptor.

The IL-1R on murine T cells is a Mr = 80,000 plasma membrane glycoprotein. cDNA cloning and transfection experiments have shown that this is an integral membrane protein, which binds both IL-1 alpha and IL-1 beta and transduces the IL-1 signal. A mAb, RM-5, which binds an epitope on the receptor which is distinct from the IL-1 binding site has been produced in rats. RM-5 has been used to immunoprecipitate the IL-1R from 32P-orthophosphate labeled CHO cells which express approximately 100,000 functional, murine rIL-1R/cell. Phosphorylation of the receptor was observed as early as 1 min after the addition of IL-1 and continued for periods of up to 30 min. Phosphorylation increases as the concentration of IL-1 increases from 10(-13) to 10(-8) M. Potassium hydroxide hydrolysis of the phosphorylated IL-1R shows that more than 90% of the phosphate is incorporated into serine or threonine. Thus, one of the earliest events after IL-1 binding to the IL-1R is activation of a serine/threonine protein kinase and phosphorylation of the IL-1R itself.

Animals↗

The murine interleukin-4 receptor: molecular cloning and characterization of secreted and membrane bound forms.

Receptors for interleukin-4 (IL-4) are expressed at low levels on a wide variety of primary cells and cultured cell lines. Fluorescence-activated sorting of CTLL-2 cells resulted in the isolation of a subclone, CTLL 19.4, which expressed 10(6) IL-4 receptors per cell. These cells were used for the purification of IL-4 receptor protein and to prepare a hybrid-subtracted cDNA probe for isolation of cDNA clones. Three classes of IL-4 receptor cDNA were identified. The first encoded a 140 kd membrane bound IL-4 receptor containing extracellular, transmembrane, and cytoplasmic domains. The second class lacked the cytoplasmic region, and the third encoded a secreted form of the receptor. All cDNA clones expressed in COS-7 cells had IL-4 binding properties comparable to the native IL-4 receptor. The soluble form of the IL-4 receptor blocked the ability of IL-4 to induce CTLL cell proliferation and may represent a regulatory molecule specific for IL-4-dependent immune responses.

Amino Acid Sequence↗

Antibody to interleukin-5 inhibits helminth-induced eosinophilia in mice.

When rodents are infected with the nematode Nippostrongylus brasiliensis, large numbers of eosinophils appear in their blood and lungs and their serum immunoglobulin E (IgE) is increased. Injection of a monoclonal antibody to interleukin-5 completely suppressed the blood eosinophilia and the infiltration of eosinophils in the lungs of parasitized mice but had no effect on serum IgE. In contrast, an antibody to interleukin-4 inhibited parasite-induced IgE but not the eosinophilia. These results show that interleukin-5 is important in eosinophil production in vivo and that IgE and eosinophil production are regulated by different cytokines produced by the TH2 subset of CD4-expressing T cells.

Animals↗

Interleukin-6 interacts with interleukin-4 and other hematopoietic growth factors to selectively enhance the growth of megakaryocytic, erythroid, myeloid, and multipotential progenitor cells.

The growth-promoting activities of interleukin-6 (IL-6) in combination with different factors were assessed in bone marrow (BM) cultures prepared from normal mice and from mice treated with 5-fluorouracil (5-FU). Effects on hematopoietic colony formation with respect to number, size, and cellular composition were evaluated. In agreement with previous reports, IL-6 acts synergistically with IL-3 to stimulate increased numbers of granulocyte/macrophage (GM) and multilineage colonies in day-2 and day-4 post-5-FU BM cultures. Furthermore, day 4 but not day 2 post-5-FU BM showed enhanced GM colony formation when stimulated with IL-6 plus interleukin-4 (IL-4) or granulocyte colony-stimulating factor (G-CSF). In contrast, IL-6 did not increase the number of colonies supported by M-CSF or GM-CSF. Nevertheless IL-6 interacted with all factors, including M-CSF and GM-CSF, to stimulate an increase in colony size. Many of these myeloid colonies attained a diameter of greater than or equal to 0.5 mm, suggesting they derive from high proliferative potential cells (HPP-CFC). The response of normal and day-8 post-5-FU BM containing high numbers of more mature progenitors was also assessed. We found IL-6 enhanced colony formation by lineage-restricted megakaryocytic and erythroid progenitors in the presence of IL-3 and IL-4 plus erythropoietin (Epo), respectively. The sum of these results shows that IL-6 interacts with a variety of factors to regulate the growth of progenitor cells at different stages of lineage commitment and maturation.

Animals↗