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Biomedical subjects

D McKenzie

Publications and source records attributed to D McKenzie.

At least 55 records · Page 3Linked to original sources
PubMed1993

Effect of T-cell receptor antagonism on interaction between T cells and antigen-presenting cells and on T-cell signaling events.

T-cell receptor (TCR) antagonism induced by complexes of antigen analogue with major histocompatibility complex (MHC) molecules results in efficient inhibition of antigen-dependent T-cell responses. We have investigated some of the possible mechanisms by which TCR antagonists bound to the MHC molecules of antigen-presenting cells (APCs) can inhibit T-cell activation. Using a nonstimulatory analogue of the antigenic peptide influenza hemagglutinin-(307-319), we showed that MHC/antagonist complexes completely inhibit very early intracellular events of antigen-dependent T-cell activation, such as inositol phosphate turnover and Ca2+ influx. In a parallel series of experiments, the effect of TCR antagonist peptide on membrane-related activation events was also investigated. It was found that MHC/antagonist complexes on the surface of APCs did not induce stable conjugates with T cells and, most interestingly, did not inhibit antigen-induced conjugate formation. Thus, our data suggest that antagonistic peptides do not interfere with the cellular events that are required for stable T-cell/APC conjugate formation but do inhibit early biochemical events required for T-cell proliferation. The data are discussed with respect to the role of surface receptor clustering in TCR antagonism.

Animals↗
PubMed1993

Persistence of viral RNA in the central nervous system of mice inoculated with MHV-4.

In order to study the role that viral persistence may play in chronic central nervous system (CNS) disease induced by murine coronaviruses, we have used the reverse transcriptase-polymerase chain reaction (RT-PCR) to study viral RNA in the brains of mice after intracerebral inoculation of JHM virus (JHMV or MHV-4). Quantitative RT-PCR showed that JHMV RNA decreased from approximately 2 ng/ug total brain RNA at day 6 post-inoculation (PI) to 0.1 pg/ug total brain RNA at 360 days PI. Double-stranded viral RNA could be detected up to day 20 PI. By the selective use of upstream or downstream primers during the RT step, it was possible to measure negative sense and positive sense JHMV RNA respectively, and we found that there was a marked rise in the ratio of positive to negative sense JHMV RNA after day 13 PI. Analysis of amplified products by dideoxy DNA sequencing showed that the characteristic mutation of our input virus (at position 3340 of gene 3) is maintained to at least day 42 PI. Taken together, these results favor a model of JHMV persistence in vivo in which viral RNA is present as double stranded forms initially and predominantly as single stranded, positive sense forms at late timepoints. Further analysis of this model in quantitative terms may contribute to our understanding of the biological significance of coronavirus persistence in the CNS.

Animals↗
PubMed1993

Cytomegalovirus pneumonia after bone marrow transplantation. Risk factors and response to therapy.

Cytomegalovirus pneumonia complicated bone marrow transplantation in 75 (63 allogeneic and 12 autologous) of 1136 recipients (Kaplan-Meier incidence 8.8%). CMV pneumonia occurred more frequently in allogeneic (12.4%) than autologous recipients (3.3%). Increased risk for CMV pneumonia was observed in allogeneic recipients who were seropositive (relative risk = 2.9), older age (RR = 1.4 per decade), those conditioned with total-body irradiation (RR = 2.7), who received antithymocyte globulin (RR = 2.9) or T cell-depleted marrow (RR = 2.7) or who had CMV viruria (RR = 4.0) or viremia (RR = 5.9). Autologous recipients were also at increased risk if they were seropositive (RR = 6.1), or developed viruria (RR = 7.0) or viremia (RR = 15.4). Thirteen of 14 untreated patients died without improvement. Prognosis was poor in patients who were ventilator-dependent at initiation of therapy (median survival 17 days), with only 1 long-term survivor. In contrast, patients ventilator-independent at initiation of therapy with ganciclovir and immunoglobulin (n = 22) had a median survival of > 274 days, with 9 long-term survivors. Ganciclovir alone or acyclovir with immunoglobulin in ventilator-independent patients was less effective (median survivals 80 and 10 days, respectively). Overall, 10 of 75 patients were surviving 10-73 months (median 47) from diagnosis; 9 of these were ventilator-independent at initiation of therapy and received ganciclovir with immunoglobulin. CMV pneumonia was less common, but was severe in autologous recipients, with only 2 of 12 surviving. CMV pneumonia remains a prominent cause of death following BMT. Early therapy with ganciclovir and immunoglobulin before respiratory failure supervenes may improve survival.

Acyclovir↗
PubMed1993

The role of alcohol providers in prevention: an evaluation of a server intervention programme.

Server intervention is a relatively new approach in the attempt to reduce the incidence of drinking and driving. Although a number of evaluations have suggested that the approach may be effective, there have been few comprehensive evaluations of such programmes. The present study utilized process evaluation techniques to assess reactions to a programme developed by the Addiction Research Foundation, and a quasi-experimental design to determine the impact of the programme on the serving practices of servers. Actors portrayed behaviours often faced by servers, and observers rated the reactions of the servers, who were unaware of the simulations, to these situations. The programme appears to have been effective in changing behaviour, in that trained servers exhibited less inappropriate responses than did untrained servers. In addition the results suggested that the programme increased servers' knowledge about their obligations and potential strategies for dealing with these situations. The implications of these findings for future implementations of such programmes are discussed.

Accidents, Traffic↗
PubMed1992

Control of mouse U1a and U1b snRNA gene expression by differential transcription.

The expression of mouse embryonic U1 snRNA (mU1b) genes is subject to stage- and tissue-specific control, being restricted to early embryos and adult tissues that contain a high proportion of stem cells capable of further differentiation. To determine the mechanism of this control we have sought to distinguish between differential RNA stability and regulation of U1 gene promoter activity in several cell types. We demonstrate here that mU1b RNA can accumulate to high levels in permanently transfected mouse 3T3 and C127 fibroblast cells which normally do not express the endogenous U1b genes, and apparently can do so without significantly interfering with cell growth. Expression of transfected chimeric U1 genes in such cells is much more efficient when their promoters are derived from a constitutively expressed mU1a gene rather than from an mU1b gene. In transgenic mice, introduced U1 transgenes with an mU1b 5' flanking region are subject to normal tissue-specific control, indicating that U1b promoter activity is restricted to tissues that normally express U1b genes. Inactivation of the embryonic genes during normal differentiation is not associated with methylation of upstream CpG-rich sequences; however, in NIH 3T3 fibroblasts, the 5' flanking regions of endogenous mU1b genes are completely methylated, indicating that DNA methylation serves to imprint the inactive state of the mU1b genes in cultured cells. Based on these results, we propose that the developmental control of U1b gene expression is due to differential activity of mU1a and mU1b promoters rather than to differential stability of U1a and U1b RNAs.

3T3 Cells↗
PubMed1992

Diagnostic concordance in functional psychosis revisited: a study of inter-relationships between alternative concepts of psychotic disorder.

More than a decade ago, a series of retrospective studies examined the concordance between proliferating definitions of severe psychiatric disorder. The European response has been a poly-diagnostic one, which has attempted to maintain interest in a broad range of psychiatric phenomena in the psychoses. In North America a more convergent approach has emerged, resulting in a series of operational definitions evolving from one another, and a correspondingly limited capacity to allow alternative perspectives to co-exist. The present study uses a prospective design as well as recent improvements in the clinical validity of psychopathology assessment to re-evaluate the relationships between competing concepts of psychotic illness in a broad sample (N = 176) of recent-onset psychotic patients. In the schizophrenic group, concordance was predictably highest among recent North American 'cousins', and lowest among various historical concepts. There was a moderately high concordance between selected schizoaffective and atypical psychosis definitions, indicating that this component is an important area for further studies of descriptive validity. These interrelationships may be used as a starting point to explore latent classes underlying the phenomena of functional psychosis.

Adult↗
PubMed1991

Medical evaluation of internationally adopted children.

BACKGROUND: Despite many reports of medical illness in children adopted from abroad, there are currently no accepted guidelines for medical evaluation of this population. METHODS: Two hundred ninety-three children adopted from 15 countries (mean age, 14.0 months; 55 percent girls) were evaluated by history taking, physical examination, and screening tests for hepatitis B virus (HBV), human immunodeficiency virus type 1, tuberculin reactivity, intestinal parasites, syphilis, excretion of cytomegalovirus, renal disease, and anemia. All but four were seen within one month of their arrival in the United States. RESULTS: Fifty-seven percent of the children (168 of 293) were found to have at least one important medical condition. Eighty-one percent of the diagnoses were established by screening test, rather than by history taking or physical examination. Infectious diseases made up the majority of the medical conditions (73 percent). Serologic testing for hepatitis B surface antigen was positive in 5 percent of the children. Characteristics associated with the acquisition of HBV infection included arrival within the first three years of the study (P = 0.017), Asian origin (P = 0.011), and receipt of a blood transfusion abroad (P = 0.008). Ten children (3 percent) had positive Mantoux skin tests, and four of these had active pulmonary tuberculosis. Tuberculin reactivity was significantly associated with older age (P less than 0.001) and lower weight (P = 0.037). Intestinal parasites were isolated from 14 percent of the international adoptees. Non-Korean adoptees were 16 times more likely to be harboring at least one intestinal parasite than were Korean adoptees (P = 0.005). CONCLUSIONS: Directed screening tests should be a routine component of the medical evaluation of all children adopted from abroad, regardless of age, sex, or country of origin.

Adoption↗
PubMed1991

Posttraumatic stress disorder following recent-onset psychosis. An unrecognized postpsychotic syndrome.

Clinical experience with psychotic patients early in the course of their illness suggested that symptoms of posttraumatic stress disorder (PTSD) may not be uncommon after recovery from an acute psychotic episode. Thirty-six patients recovering from an acute psychotic episode within 2 to 3 years of onset of their illness were assessed as inpatients and followed up on two occasions during the year after discharge. The prevalence of PTSD was found to be 46% at 4 months and 35% at 11 months, measured by a questionnaire linked to DSM-III criteria. The relationships between negative symptomatology and PTSD symptoms and between depressive symptomatology and PTSD symptoms were also examined; a significant correlation was found only for the latter. The psychopathological, preventive, and therapeutic implications of these findings are discussed, and future research strategies are proposed.

Acute Disease↗
PubMed1991

A review of nursing manpower issues.

This paper, presented by the E.C. Hospital Committee's Sub-Committee on Economics and Planning, reviews what is regarded by many as a crisis in hospital nurse manpower in the 1990's. Indeed, there are signs that the problem of recruiting sufficient qualified staff had already arrived in some places in the latter part of the 1980's. So what is the nature and extent of the problem? Information has been gathered about population, as it affects demands on health care and as a source of potential health service employees. The current position of nurse staffing has been investigated and is discussed together with indications from member states of ways of tackling the problem to safeguard the quality of patient care to which the member states are committed.

Data Collection↗
PubMed1990

Prolactin response to low-dose haloperidol challenge in schizophrenic, non-schizophrenic psychotic, and control subjects.

Haloperidol was administered IV to 46 male psychotic inpatients and 28 male control subjects. A two-way analysis of covariance, with age as the covariate, revealed that DSM-III schizophrenics (n = 27) had a lower prolactin response to haloperidol than did the controls (n = 28). There were no significant differences between the prolactin responses in schizophrenics, patients with affective disorders (n = 7), and those with other psychoses (n = 12), which included patients with paranoia, schizophreniform, schizoaffective disorder, and atypical psychoses. These findings support the proposition that tuberoinfundibular dopaminergic dysfunction may occur in certain patients with DSM-III schizophrenia.

Adult↗
PubMed1988

Alloantigen presentation by B cells. Requirement for IL-1 and IL-6.

We have evaluated the requirements for non-activated allogeneic B cells to present alloantigen in primary MLC. We found that the generation of an MLR was dependent on the addition of exogenous IL-1 and IL-6 to the cultures; neither lymphokine by itself was capable of significantly stimulating the response. Our results suggest that the concentration of these lymphokines present in a standard MLR culture may serve to regulate the magnitude of the proliferative response. The B cells that co-stimulated with IL-1 and IL-6 were found to be contained almost exclusively within the large, low density population. Presumably, large low density B cells have attained a state in which they are particularly effective at presentation of alloantigen. Together our findings indicate that three components are required for Ag presentation in primary MLC: class II MHC-positive stimulator cells that have attained the appropriate state of differentiation and the presence of both IL-1 and IL-6.

Adjuvants, Immunologic↗
PubMed1988

Role of antigen in the B cell response. Specific antigen and the lymphokine IL-5 synergize to drive B cell lymphoma proliferation and differentiation to Ig secretion.

CH12 tumor B cells specific for SRBC require SRBC as Ag and the lymphokine IL-5 (formerly known as BCGFII) for optimal proliferation and differentiation to Ig-secreting cells. Lysed SRBC and IL-5 purified to homogeneity synergize markedly, especially at low B cell densities. A sizable proportion of CH12 cells differentiate into Ig-secreting plaque-forming cells when low numbers of the B lymphoma cells (100 to 3000) are cultured with Ag and IL-5. IL-2 or IL-4 have no effects. Intact SRBC or lysed SRBC are equally effective as sources of Ag. Even in the presence of the mitogens LPS and dextran sulfate, there is a striking requirement for Ag for both proliferation and differentiation at low B cell density. Because of the low cell numbers used, the results strongly suggest that the effects of Ag and lymphokine are directly on the B cell. The cell surface phenotype of the CH12 lymphoma and the kinetics of their response suggest that CH12 B cells have the characteristics of activated B cells. Thus, it appears that Ag binding to surface Ig gives a direct signal to at least some B cells that is critical in the later phases of the B cell response after initial activation during which proliferation and differentiation to Ig secretion occur and that the lymphokine IL-5 costimulates with Ag to mediate this phase of the response.

Adjuvants, Immunologic↗
PubMed1988

Metastatic extramammary Paget's disease: dramatic response to combined modality treatment.

A case of extramammary Paget's disease is reported. The distinguishing features of the case are: (1) localization of the primary lesion to the scrotum, (2) development of metastases in the absence of a recognizable underlying carcinoma, and (3) response of the systemic disease to a combination of radiation therapy and chemotherapy. The histogenesis, clinical behavior, and treatment of extramammary Paget's disease are reviewed.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1988

Longitudinal study of untreated periodontitis (II). Microbiological findings.

11 volunteer subjects with advanced chronic periodontitis participated in a 1-year longitudinal clinical and microbiological study. Subgingival plaque was collected at each of 7 visits from 148 pre-selected sites in the left jaw quadrants (test sites) and on the first and last visits, only from 117 sites in the left jaw quadrants (control sites). All sites were examined clinically at each of the 7 visits, and the microbiological markers investigated were the % spirochaetes and % black pigmented Bacteroides species in subgingival plaque. At the completion of the study, the sequential changes in probing attachment level at each site were subjected to regression analysis to determine the direction and extent of attachment change. Possible correlations between attachment change and % spirochaetes or % black-pigmented bacteroides were investigated using both individual sites and individual subjects. No significant differences were observed in either of the microbial variables between test and control sites. Possible correlations between the microbiological markers and attachment changes were investigated at baseline, at the 12-month visit and using the microbial data accumulated over all 7 visits. Significant differences were observed only at the 12-month visit when the % spirochaetes of both test and control sites were significantly lower in subjects showing the greatest improvement in attachment level. Overall, these results indicate that quantification of either spirochaetes or black-pigmented Bacteroides species cannot be used reliably to identify or predict disease-active sites.

Adult↗