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Biomedical subjects

D E Johnson

Publications and source records attributed to D E Johnson.

At least 73 records · Page 4Linked to original sources
PubMed2000

Programmed cell death regulation: basic mechanisms and therapeutic opportunities.

The molecular mechanisms responsible for induction or inhibition of apoptosis signal transduction have been intensively investigated during the past few years. Information gained from mechanistic studies and from structural analysis of apoptosis regulatory proteins has provided considerable insight into the pathways that determine whether a cell will live or die. Many of these advances were recently presented at the American Association for Cancer Research Special Conference on 'Programmed Cell Death Regulation: Basic Mechanisms and Therapeutic Opportunities'. This mini-review will discuss the current state of knowledge regarding apoptosis signaling pathways and the function of apoptosis regulatory proteins.

Apoptosis↗
PubMed2000

Noncaspase proteases in apoptosis.

Biochemical and genetic analysis of apoptosis has determined that intracellular proteases are key effectors of cell death pathways. In particular, early studies have pointed to the primacy of caspase proteases as mediators of execution. More recently, however, evidence has accumulated that noncaspases, including cathepsins, calpains, granzymes, and the proteasome complex, also have roles in mediating and promoting cell death. An important goal is to understand the importance of distinct noncaspases in various forms of apoptosis, and to determine whether pathways mediated by noncaspase proteases intersect with those mediated by caspases. In this review the roles of noncaspase proteases in the biochemistry of apoptosis will be discussed.

Animals↗
PubMed2000

The role of cytotoxic necrotizing factor-1 in colonization and tissue injury in a murine model of urinary tract infection.

Cytotoxic necrotizing factor-1 (CNF1) is commonly found in Escherichia coli isolates from patients with urinary tract infection (UTI). To determine whether CNF1 is an important UTI virulence factor we compared the ability of a clinical E. coli UTI isolate and a CNF1-negative mutant of that isolate to colonize and induce histological changes in the urinary tract in a murine model of ascending UTI. We found no evidence that the mutant strain was attenuated.

Animals↗
PubMed2000

Chronic fatigue syndrome: sociodemographic subtypes in a community-based sample.

Most chronic fatigue syndrome (CFS) studies are based on information about patients from primary or tertiary care settings. These patients might not be typical of patients in the general population. This investigation involved examinations of individuals with CFS from a community-based study. A random sample of 18,675 in Chicago was interviewed by telephone. Individuals with chronic fatigue and at least four minor symptoms associated with CFS were given medical and psychiatric examinations. A group of physicians then diagnosed individuals with CFS, who were then subclassified based on three sociodemographic categories--gender, ethnicity, and work status. Sociodemographic subgroups were analyzed in terms of symptom severity, functional disability, coping, optimism, perceived stress, and psychiatric comorbidity. Women, minorities, and nonworking individuals with CFS reported greater levels of functional disability, symptom severity, and poorer psychosocial functioning than men, Caucasians, and working individuals, suggesting sociodemographic characteristics may be associated with poorer outcomes in urban, community-based samples of CFS individuals.

Adolescent↗
PubMed2000

Counseling dilemmas in EEC syndrome.

In this report we describe a prenatally diagnosed case with four-limb ectrodactyly and cleft lip/palate. The family history reveals three-generation oligodontia. The difficulties in counseling of the families with EEC syndrome are discussed.

Abnormalities, Multiple↗
PubMed2000

p21WAF1 prevents down-modulation of the apoptotic inhibitor protein c-IAP1 and inhibits leukemic apoptosis.

BACKGROUND: Prior studies indicate that leukemias expressing high levels of the p21WAF1 cell cycle inhibitor have a poorer prognosis than p21WAF1-negative leukemias. Although p21WAF1 is upregulated by p53 in the setting of DNA damage, the prognostic significance of p21WAF1 is independent of p53 status. The molecular basis of the negative prognostic effect of p21WAF1 remains obscure, but it is believed to result from decreased apoptosis of p21WAF1-expressing leukemias. MATERIALS AND METHODS: We studied the effects of p21WAF1 on apoptosis of K562 leukemic cells, which lack wild-type p53 and do not express endogenous p21WAF1. An inducible p21WAF1 system was used and the effect of p21WAF1 induction on susceptibility to etoposide-mediated apoptosis was measured. RESULTS: p21WAF1 decreased apoptotic death of K562 leukemic cells in response to etoposide. Analysis of intermediaries in the apoptotic pathway indicated that p2 WAF1 had no effect on cytochrome c release or cleavage of procaspase-3. In contrast, p21WAF1 was protective against cleavage of caspase targets poly(ADP-ribose)polymerase (PARP), retinoblastoma protein (Rb), and lamin. The expression of the inhibitor of apoptosis protein c-IAP1, which inhibited the function of executioner caspases 3 and 7, was studied. c-IAP1 protein expression was found to be present in a majority of leukemic blasts from untreated patients, but absent in normal differentiating myeloid progenitor cells. In K562 cells, treatment with etoposide in the absence of p21WAF1 induction resulted in post-transcriptional down-modulation of c-IAP1 levels. c-IAP1 loss involved proteasomal, rather than caspase, degradation pathways. Expression of p21WAF1 sustained c-IAP1 protein levels in the presence of etoposide. CONCLUSIONS: Etoposide-mediated apoptosis involves down-modulation of the anti-apoptotic protein c-IAP1. Our findings support the hypothesis that p21WAF1 contributes to leukemic chemoresistance by stabilizing c-IAP1 levels in the presence of chemotherapy.

Antineoplastic Agents, Phytogenic↗