Biological characteristics of newly diagnosed poor prognosis acute myelogenous leukemia

A pilot study was conducted of the biological characteristics of the leukemia cells of newly diagnosed patients with poor prognosis acute myelogenous leukemia (AML). This study included measurements of the pretherapy proliferative rate of the leukemia cells in vivo, assessment of differentiation in vivo during remission induction therapy, and the level of expression of the fms, myc, and IL1β genes in pretherapy leukemia cells. Short cell cycle times were characteristic of the best prognostic category and were associated with a rapid reduction in marrow leukemia cells in cytosine arabinoside (araC)-sensitive patients. Expression of c-fms was associated with rapid reduction in marrow leukemia cells during araC therapy and with a successful treatment outcome. Expression of the IL1β gene was associated with short remissions. These studies suggest that when compared to newly diagnosed standard prognosis AML, the leukemia of poor prognosis patients is more likely to exhibit long cell cycle times, low levels of fms expression, and is less likely to be associated with myeloid differentiation during remission induction therapy. © 1993 Wiley-Liss, Inc.     

Fast-phase instabilities in normally sighted relatives of congenital nystagmus patients—autosomal dominant and x-chromosome recessive modes of inheritance

Verification of inheritance in congenital nystagmus (CN) is only possible through the identification of more than one affected member in a family, since in a single case there are no accurate clinical differentiations between spontaneous and inherited CN. We performed electronystagmographic examinations (ENG) to search for abnormal involuntary eye movements as a sign of heredity in seemingly unaffected members of CN families.ENG registrations were performed under three test conditions: (1) with the subject fixating a target, (2) with the room lights off and (3) with closed eyes.Fifty normally sighted individuals (group (a) underwent the test procedure to provide a baseline of normality. Five CN families (three dominant, two sex-linked recessive) were tested as group (b). The eye movement recordings were analysed in terms of nystagmus intensity (amplitude x frequency of the involuntary saccade). In every one of the five families, abnormalities in seemingly non-affected members could be demonstrated: in four families, fastphase instabilities, in the fifth family a true (CN) (slowphase instability).All certain gene carriers were diagnosed correctly by the ENG.These findings indicate a method for detecting slightly affected members in dominant pedigrees and female gene carriers in sex-linked mode of transmission.     

Comfort. Immigrant Hispanic cancer patients' views.

This study focuses on the meaning of comfort from the perspective of immigrant Hispanic cancer patients undergoing treatment at a large Western medical center. Patients (n = 10), in 30 ethnographical interviews conducted in Spanish by a culturally sensitive interviewer identified characteristics, needs, and sources of comfort. The characteristics of comfort were: feeling integrated, functioning and normalcy, care and nurturing, security and safety, control and "comodo." Comfort needs evolved into 6 categories: nurturing, familiar environment, safety, quality of life, normalcy, and "animo." Providers of comfort, as perceived by these Hispanic patients were: self, family, health care providers, and God. The characteristics of comfort most frequently talked about by the Hispanic participants were feeling integrated and nurtured. Integrated, a seemingly complex characteristic of comfort, reflected a sense of inner peace with oneself that went beyond the physical comfort. Function and normalcy were also perceived to be important aspects of comfort. It is important to note that the Hispanic patients on occasion used culturally relevant terms, such as comodo and animo (neither of which are readily translated into English) to convey their impressions of comfort. The study demonstrates that comfort is important in illness and cancer treatment situations, and that for these Hispanic patients it also had influence from their culture.     

Flat crossed-coil detector for blood flow measurement using nuclear magnetic resonance

A new flat crossed-coil nuclear magnetic resonance (n.m.r.) detector can be used to measure flood flow at many regions of the body, is introduced. It is compared, bothin vitro andin vivo, with the already proven cylindrical crossed-coil n.m.r. detector. Both detectors use a single high-field homogenous magnet. A single-sideband receiver reduces the effect of transmitter leakage into the receiver coil to allow the use of a high-level transmitter field. Preliminary application of the flat crossed-coil detector to the detection of cerebral blood flow is presented.     

Reconstitution of a functional interleukin (IL)-7 receptor demonstrates that the IL-2 receptor γ chain is required for IL-7 signal transduction

The interleukin (IL)-2 receptor γ chain has recently been shown to be a component of the IL-7 and IL-4 receptors. Using a transient transfection assay and the trans-activation of reporter gene constructs which are under the control of cytokine-responsive promoter elements, we have studied signal transduction through the IL-7 receptor (IL-7R). The reporter gene expression was not stimulated by receptors that contained the cytoplasmic domain of the IL-7R, either as intact IL-7R or as part of a chimeric receptor. However, co-expression of the IL-7R with the IL-2 receptor γ chain was able to stimulate gene activation. For maximal stimulation the intact cytoplasmic domains of each chain was required.     

Molecular cloning of a ligand for the inducible T cell gene 4-1BB: a member of an emerging family of cytokines with homology to tumor necrosis factor

4-1BB is an inducible T cell antigen that shows sequence homology to members of an emerging family of cytokine receptors, including those for tumor necrosis factor and nerve growth factor. To aid in the analysis of the function of 4-1BB we have utilized a soluble form of the molecule as a probe to identify and clone the gene which encodes its ligand. The ligand for 4-1BB is a type II membrane glycoprotein that has homology to tumor necrosis factor, lymphotoxin, and the ligands for CD40 and CD27, all of which are themselves ligands to receptors in this superfamily. The gene for 4-IBB is on mouse chromosome 4 and maps close to the p80 form of the tumor necrosis factor receptor as well as the gene for CD30. The gene for 4-IBB ligand maps to mouse chromosome 17, but considerably distal to the tumor necrosis factor and lymphotoxin genes. Interaction of 4-1BB with its ligand induces the proliferation of activated thymocytes and splenic T cells, a response which is mimicked on similar cell populations stimulated with an antibody to 4-1BB.     

Education modifies the effect of apolipoprotein epsilon 4 on cognitive decline

OBJECTIVES: To assess the influence of education on the association between apolipoprotein E and cognitive change. DESIGN: Prospective cohort. PARTICIPANTS: HMO-based sample of 2168 non-demented community-dwelling elderly followed over 6 years. MEASUREMENTS: Generalized estimating equations were used with the difference between baseline and follow-up cognitive abilities screening instrument (CASI) as the outcome variable. RESULTS: At follow-up, 6% of the sample had a decline of 1.5 S.D. or greater on the CASI. Compared to individuals without an APOE4 allele, individuals with a single APOE4 allele did not have greater CASI decline. By contrast, individuals with two APOE4 alleles experienced greater decline in cognitive performance and the magnitude of that decline decreased as years of educational attainment increased. These relationships held after adjusting for age, gender, ethnicity, depression, diabetes, and history of vascular disease. CONCLUSION: Lower education was associated with steep 4-year cognitive decline for APOE4 homozygotes but not for APOE4 heterozygotes. Potentially modifiable host factors such as education could influence the association of high-risk genotypes and cognitive decline.