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Biomedical subjects

K W Johnson

Publications and source records attributed to K W Johnson.

14 recordsLinked to original sources
PubMed1992

In vivo evaluation of an electroenzymatic glucose sensor implanted in subcutaneous tissue.

Cleanroom processing techniques have been used to mass-produce flexible, electroenzymatic glucose sensors designed for implantation in subcutaneous tissue. In vitro characterization studies have shown the sensor's performance to be acceptable. Initial in vivo studies were conducted with the sensor implanted in the subcutaneous tissue of rabbits. Sensors implanted in the subcutaneous tissue of normal human subjects showed an excellent correlation between glucose concentrations measured by the sensor and capillary finger sticks measured with a commercial analyzer.

Animals↗
PubMed1992

Survival in adult leukaemia.

The evaluation of treatment and outcome in adult leukaemia requires unselected data. Such data is available from one Health Region in the United Kingdom with an adult population of 3.1 million. In the period July 1982 to December 1989, 676 cases of acute myeloid leukaemia (AML), 136 of acute lymphoblastic leukaemia (ALL) and 141 of chronic granulocytic leukaemia (CGL) were registered. The median survival for AML was 21 weeks and 26% of these patients died within 4 weeks of diagnosis. For ALL, the corresponding figures were 81 weeks and 21%. In CGL, the median survival was significantly different for males and females: 113 weeks and 173 weeks respectively. The 5-year survival in AML was 9%, in ALL, 31% and in CGL, 29% (20% for males, 45% for females). Age at presentation was the single most powerful prognostic factor and probably accounts for survival differences between patients referred to tertiary centres and those treated in district general hospitals. (DGH). Survival may be improving overall as supportive care improves.

Acute Disease↗
PubMed1992

Supporting the elderly: workplace programs for employed caregivers.

An aging population and extended longevity are increasing the number of older people needing informal and family support. At the same time, women, the traditional caregivers, have entered the work force in record numbers. Consequently, concerns about how to care for dependent family members have become workplace issues. In response to the needs of employees who care for family members, employers have produced an array of policies, benefits, and programs, including flexible work schedules and information and referral services. Although these programs are a valuable complement to community services and government initiatives, relatively few employers have recognized the potential effects of caregiving on absenteeism, productivity, and turnover; even fewer have responded with workplace programs directed to the needs of their caregiving employees. To fill the gap, the government is considering mandating employee benefits, such as leave time for family illness. Community services are increasingly being directed to the needs of older people and their caregivers.

Absenteeism↗
PubMed1991

Molecular cloning of a novel human cdc2/CDC28-like protein kinase.

A homology probing approach was utilized to isolate a new human protein kinase. Deoxyoligonucleotide probes recognizing a conserved subdomain in the COOH-terminal portion of protein kinases identified a cDNA clone encoding a putative kinase with predicted serine/threonine phosphorylation specificity. The full-length, 1.7-kilobase pair cDNA hybridizes to 1.7- and 3.4-kilobase mRNA transcripts in a number of tissues. The size of the encoded protein is 454 amino acids and consists of an NH2-terminal 130-residue segment, which may represent a regulatory region, followed by a 324-residue catalytic domain. Comparisons and alignments of the primary sequence and predicted secondary structure of the catalytic region to other known kinases reveal that the new kinase, denoted "CLK" (for CDC-like kinase), represents a prototype for a new family of human protein kinases bearing significant homology to the yeast cdc2/CDC28 kinases that regulate the cell cycle.

Amino Acid Sequence↗
PubMed1990

cAMP regulation of IL-2 receptor expression. Selective modulation of the p75 subunit.

As previous experiments have shown that IL-2 activity is abrogated by cAMP, its effect on IL-2R expression by normal and leukemic T lymphocytes was evaluated in detail. The exposure of murine or human T cells to dibutyryl cAMP or the cAMP-elevating drug, forskolin, resulted in a decrease in high affinity IL-2 binding. Equilibrium binding analyses revealed that elevation of cAMP for 4 to 5 h produced a 40 to 50% decrease in the number of detectable receptors, whereas the affinity of the IL-2R interaction remained unchanged. The effect of cAMP could be attributed to a selective effect on the 75-kDa chain of the IL-2R (p75) subunit of the 55-kDa chain of the IL-2R/p75 heterodimer. The mechanism for the decreased expression of high affinity IL-2R appears to be due to a dual effect of cAMP, which functions to both increase the rate of IL-2R internalization, and to decrease the rate of expression of new receptors. Moreover, the effect of cAMP on IL-2 binding to p75 subunits is post-transcriptional, because the steady state levels of p75 mRNA expression are not altered within a time interval that produced nearly a 50% reduction in p75 binding.

Animals↗
PubMed1988

cAMP antagonizes interleukin 2-promoted T-cell cycle progression at a discrete point in early G1.

T lymphocytes are stimulated to proliferate in an autocrine/paracrine manner by the lymphokine interleukin 2 (IL-2). In seeking further insight into the mechanisms by which IL-2 induces progression of T cells through the G1 phase of the cell cycle, studies were performed with agents that increase cellular adenosine 3',5'-cyclic monophosphate (cAMP), a well-known inhibitor of lymphocyte growth. The addition of dibutyryl-cAMP, cholera toxin, forskolin, or 3-isobutyl-1-methylxanthine to an IL-2-dependent murine T-cell line evoked a dose-related suppression of S-phase transition without affecting cellular viability. Moreover, elevation of cAMP levels led to an accumulation of uniformly small cells, suggesting an arrest in early G1. Consistent with these findings, dibutyryl-cAMP inhibited the incorporation of both [3H]-uridine and [3H]thymidine by IL-2-stimulated, synchronized normal human T cells. Furthermore, maximal inhibition occurred during early G1, as indicated by experiments where the addition of dibutyryl-cAMP was delayed with respect to IL-2 stimulation. Quantitative flow cytometric analysis of RNA and DNA content of IL-2-stimulated cells affirmed that increased cAMP inhibits RNA accumulation and S-phase transition. In addition, exposure of IL-2-dependent, asynchronously proliferating normal human T cells to dibutyryl-cAMP resulted in uniform growth arrest in early G1, the point at which cycling T cells accumulate when they are deprived of IL-2. These results indicate that increased cAMP inhibits G1 progression stimulated by IL-2 and provide a rationale for the use of cAMP analogues as pharmacologic probes for the dissection of molecular events occurring during IL-2 signaling and T-cell G1 transit. They also suggest the possibility of therapeutic immunosuppression by a combination of agents that act at different stages of the T-cell cycle.

Bucladesine↗
PubMed1987

Primary cellular target responsible for dimethylnitrosamine-induced immunosuppression in the mouse.

The present studies were undertaken to identify the cellular targets responsible for immunosuppression by dimethylnitrosamine (DMN). The in vitro antibody responses of splenocytes from B6C3F1 mice exposed to 6 mg/kg DMN for 7 days to the T cell-independent antigen dinitrophenyl-Ficoll and the T cell-dependent antigen sheep erythrocytes were used for separation and reconstitution studies. The antibody-forming cell response of spleen cells from DMN-treated mice to the T-independent and T-dependent antigens was suppressed by 72% and 61%, respectively, when compared to vehicle controls. Whole spleen suspensions were fractionated into nonadherent populations by plastic adherence and Sephadex G-10 depletion of macrophages. Adherent antigen-presenting cells were obtained by incubating spleen suspensions in culture wells and removing nonadherent cells after 3 h. By combining vehicle and DMN nonadherent and adherent populations it was demonstrated that the population most affected by DMN exposure in both the sheep erythrocyte and dinitrophenyl-Ficoll responses was the nonadherent population. The lack of T cell dependence of the dinitrophenyl-Ficoll response was verified by elimination of T cells from whole spleen suspensions by monoclonal anti-thy 1.2 antibody plus complement treatment. These results indicated the B cell from DMN-treated mice as the splenic cell type responsible for suppressed antibody-forming cell responses to dinitrophenyl-Ficoll. B cells, T cells (prepared by cytotoxic elimination of B cells using anti-immunoglobulins) and adherent antigen-presenting cells (macrophages) from vehicle- and DMN-treated mice were fractionated and recombined and immunized with sheep erythrocytes (requires B cell, T cell, and macrophage cooperation). While splenic macrophages from DMN-treated mice supported control responses, T-helper activity was slightly reduced and B cell function was especially impaired. The conclusion that T cell function was less suppressed was supported by control responses of DMN-treated mice to concanavalin A but reduced responsiveness to lipopolysaccharide under conditions of limiting cell densities. These studies indicate that the primary cellular target of DMN exposure resulting in suppressed antibody responses is the B lymphocyte.

Animals↗