Biomedical subjects

Peter Johnson

Publications and source records attributed to Peter Johnson.

26 records · Page 2Linked to original sources

PubMed2003

The mechanisms of action of rituximab in the elimination of tumor cells.

The anti-CD20 chimeric monoclonal antibody rituximab kills B cells by multiple mechanisms, including complement-dependent cytoxicity, antibody-dependent cellular cytotoxicity, and induction of apoptosis. Rituximab can also sensitize cells to the effects of chemotherapy. To optimize treatment of non-Hodgkin's lymphoma and improve response rates, a fuller understanding of these mechanisms and their relative contributions to clinical efficacy is required. Therefore, this has been an area of active research in recent years. Preclinical studies have established that the human Fc region of rituximab is important in mobilizing antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity effector mechanisms. In addition, molecular consequences of CD20 binding, including redistribution of membrane lipid "rafts," activation of src kinases, phospholipases and caspases, and down-regulation of interleukin-10, have been identified. Clinical studies have also identified differences in patients' responses to rituximab associated with Fc receptor polymorphisms, and increases in enzymes involved in apoptotic pathways have been seen in the lymphocytes of patients following rituximab treatment. This article reviews the current understanding of the mechanisms of rituximab cell killing in the light of the latest clinical and preclinical data.

Animals↗

PubMed2003

Social barriers to emotional expression and their relations to distress in male and female cancer patients.

OBJECTIVE: Emotional expression is an important means of coping with stressful experiences such as cancer. Social barriers to expression may have adverse effects. Research has suggested that men are less likely to express their emotions and have different patterns of social support compared to women. We examined whether male cancer patients have a lower tendency to express emotions, are less likely to perceive social barriers to expression, and are differentially affected by social barriers from different support sources as compared to women. DESIGN: Questionnaires were administered to 41 women and 41 men using a cross-sectional study design. METHOD: Patients diagnosed with gynaecological or prostate cancer within the past 5 years completed questionnaires on moods, intrusive thoughts, social constraints and emotional expressivity. RESULTS: There was a trend towards greater emotional expressivity in women as compared to men, but no significant gender differences in perceptions of social constraints from spouse/partner or others. Multiple regression analyses revealed that men experienced significantly greater distress in association with social constraints from their spouse/partner than did women. CONCLUSION: Men may be more vulnerable to social barriers to expression than previously assumed. Gender differences in emotional expressivity may be less important than the social context in which expression takes place.

Adaptation, Psychological↗

PubMed2002

Acquisition of potential N-glycosylation sites in the immunoglobulin variable region by somatic mutation is a distinctive feature of follicular lymphoma.

Most patients with follicular lymphoma (FL) have somatically mutated V genes with intraclonal variation, consistent with location in the germinal center site. Using our own and published sequences, we have investigated the frequency of potential N-glycosylation sites introduced into functional V(H) genes as a consequence of somatic mutation. FL cells were compared with normal memory B cells or plasma cells matched for similar levels of mutation. Strikingly, novel sites were detected in 55 of 70 (79%) patients with FL, compared to 7 of 75 (9%) in the normal B-cell population (P <.001). Diffuse large B-cell lymphoma (DLCL) showed an intermediate frequency (13 of 32 [41%] patients). Myeloma and the mutated subset of chronic lymphocytic leukemia showed frequencies similar to those of normal cells in 5 of 64 (8%) patients and 5 of 40 (13%) patients, respectively. In 3 of 3 random patients with FL, immunoglobulin was expressed as recombinant single-chain Fv in Pichia pastoris, and glycosylation was demonstrated. These findings indicate that N-glycosylation of the variable region may be common in FL and in a subset of DLCL. Most novel sites are located in the complementarity-determining regions. V(H) sequences of nonfunctional V(H) genes contained few sites, arguing for positive selection in FL. One possibility is that the added carbohydrate in the variable region contributes to interaction with elements in the germinal center environment. This common feature of FL may be critical for tumor behavior.

Amino Acid Sequence↗

PubMed2002

Antioxidant enzyme expression in health and disease: effects of exercise and hypertension.

Antioxidant enzymes (superoxide dismutases, catalase and glutathione peroxidase) are components of an organism's mechanisms for combating oxidative stress which is generated in normal metabolism and which may also be a reaction in response to external stimuli. This review identifies the general significance of antioxidant enzymes in health and disease, and some of the diseases that are now believed to have oxidative stress as a component. A discussion is then presented of the molecular mechanisms by which antioxidant enzyme expression is controlled at the transcriptional and post-transcriptional levels. The final sections of the review highlight the effects of exercise and hypertension on antioxidant enzyme expression in a number of different tissues, and the possibilities for future studies in these areas are discussed.

Animals↗

PubMed2002

Mechanism of action of rituximab.

Rituximab, the humanized chimeric anti-CD20 monoclonal antibody, represents a powerful tool for treating B-cell malignancies and is licensed for the treatment of relapsed or chemorefractory low-grade or follicular non-Hodgkin's lymphoma (NHL). It has a unique mode of action and can induce killing of CD20+ cells via multiple mechanisms. The direct effects of rituximab include complement-mediated cytotoxicity and antibody-dependent cell-mediated cytotoxicity, and the indirect effects include structural changes, apoptosis, and sensitization of cancer cells to chemotherapy. In vitro studies have made a significant contribution to the understanding of these mechanisms of action and have led to the development of innovative and effective treatment strategies to optimize patient response. The most significant of these strategies is the combination of rituximab and CHOP chemotherapy (cyclophosphamide, doxorubicin, vincristine and prednisone), which is proving a highly effective combination in the treatment of NHL. However, all patients do not respond equally well to rituximab, and in vitro studies have identified a possible mechanism of resistance involving the anti-complement inhibitors CD55 and CD59. Neutralizing antibodies to CD55 and CD59 can overcome resistance to rituximab-mediated complement-mediated cytotoxicity in vitro. This paper overviews our understanding of the mechanisms of action of rituximab and identifies how this knowledge could be applied in a clinical setting to maximize response in both sensitive and resistant patients.

Antibodies, Monoclonal↗

PubMed2002

Spontaneous clinical regression in chronic lymphocytic leukaemia.

Chronic lymphocytic leukaemia (CLL) is a B-cell disorder, which has a median survival of over 10 years from diagnosis for stage A disease. The natural history of stage A disease is generally indolent or only slowly progressive. It is less well known that CLL may undergo spontaneous regression. We report a series of 10 such cases (eight stage A and two stage B) followed at our institutions.

Aged↗

PubMedDate not supplied

The 1999-2000 task analysis of American nurse-midwifery/midwifery practice.

A master list of tasks, which contained 200 task statements, 23 professional issues statements, and 177 clinical conditions, was divided into three equivalent survey forms and distributed to those certified nurse-midwives (CNMs) and certified midwives (CMs) certified by the ACNM Certification Council, Inc. during the 5-year period from 1995 to 1999. Specific efforts were made to encourage the participation of CMs, because they represented a new professional cohort. A total of 627 valid responses were obtained. Reasonably similar numbers of respondents contributed data related to each of the three versions of the survey form. The responsibilities have expanded substantially within the domains of nonreproductive primary health care and gynecologic care of the well woman, including advances in assisted reproductive technology. A diminished emphasis on the CNM/CM role in the provision of newborn care was documented. The ACC Research Committee recommended the revision of the entry-level certification examination blueprint, and this was approved by the ACC Board of Directors. The specific recommendations included the development of a new primary care domain and the reconfiguration of content emphasis with percentage allocations as follows: Primary Care, 5-10%; Well-Woman/Gynecology, 15-20%; Newborn, 5-10%; Postpartum, 5-10%; Antepartum, 25-30%; Intrapartum, 25-35%; Professional Issues, up to 5%.

Adult↗

PubMedDate not supplied

Multicenter retrospective analysis of the solid-screw ITI implant for posterior single-tooth replacements.

PURPOSE: This report involves the retrospective analysis of ITI implants placed and/or restored by a group of 7 clinicians located throughout the United States (5 periodontists and 2 prosthodontists). MATERIALS AND METHODS: Six hundred seventy-five posterior single-tooth implants were restored in 471 patients (average time of loading 21.30 months, with a range of 1 to 78 months). Three hundred seventy implants and 71 implants were placed in mandibular and maxillary molar sites, respectively, and 108 and 126 were placed in mandibular and maxillary premolar sites, respectively. RESULTS: A cumulative survival rate of 99.1% was obtained for all sites (6 failures). The survival rates for individual sites were as follows: 98.4% mandibular molars, 100% maxillary molars, 100% mandibular premolars, and 100% maxillary premolars. "At-risk" implants (1 to 2 mm of radiographic bone loss) were noted at 5 sites. DISCUSSION: Minimal restorative problems were found with either screw-retained (n = 71) or cemented restorations on solid abutments (n = 600); 80.3% of screw-retained and 98.2% of cemented restorations were free of complications, respectively. Patient satisfaction scores were high (97.4%) as determined by the Patient Satisfaction Questionnaire. CONCLUSION: The data suggest that solid-screw (4.1 or 4.8 mm wide) ITI implants can be a satisfactory choice for posterior single-tooth restorations.

Bicuspid↗