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Biomedical subjects

F Lynch

Publications and source records attributed to F Lynch.

At least 37 records · Page 2Linked to original sources

Pulmonary function during and after total hip replacement. Findings in patients who have insertion of a femoral component with and without cement.

Eleven patients who had a femoral component inserted with cement and twenty-three who had a femoral component inserted without cement were studied prospectively for changes in the pulmonary shunt associated with total hip replacement. The levels of oxygen in the arterial blood and the platelet counts were measured preoperatively and each morning for three days after the arthroplasty. Levels of oxygen in the arterial blood were determined intraoperatively, once before and once after the femoral component was inserted. Intraoperative shunt values increased 28 per cent when a femoral component was inserted with cement (p < 0.05), but they did not change when cement was not used. The average postoperative shunt values were higher than the average preoperative shunt values for both groups of patients, but only the values on the second postoperative day after a procedure with cement were significantly higher (p < 0.05). The ability of the patient to tolerate an increase in pulmonary shunt should be assessed when the femoral component is to be cemented during total hip replacement.

Aged↗

Activation requirements of newborn thymic gamma delta T cells.

We have analyzed the requirements for the induction of proliferative responses by thymic CD4-CD8- gamma delta T cells. Enriched populations of CD4-CD8- thymocytes from newborn mice, purified by negative selection with anti-CD4, anti-CD8, and anti-TCR alpha beta mAbs were found to contain approximately 20% gamma delta T cells that were p55IL-2R-. When these cells were cultured with a panel of lymphokines (IL-1, -2, -4, and -7), a small response was observed to some of the cytokines tested individually; however, combinations of certain lymphokines (IL-1 + 2, IL-1 + 7, and IL-2 + 7) were found to induce significant proliferation and the selective outgrowth (75-90%) of gamma delta T cells. These cells were IL-2R+, remained CD4-, yet expressed variable levels of CD8. A limited analysis with specific anti-V gamma and V delta mAb suggested that there had not been a selective expansion of preexisting V gamma 2, V gamma 3, or V delta 4 populations in response to the stimulatory lymphokine combinations. Thymic CD4-CD8- gamma delta T cells were unresponsive to stimulation with immobilized anti-pan gamma delta mAb alone. However, in the presence of immobilized anti-pan gamma delta mAb and IL-1, IL-2, or IL-7, but not IL-4, a vigorous proliferative response was observed. Phenotypic analysis showed that 80 to 95% of the proliferating cells were polyclonally expanded gamma delta T cells, expressed the p55IL-2R, and the majority remained CD4-CD8-. Blocking studies with anti-IL-2R mAb showed that stimulation with anti-pan gamma delta + IL-1, but not anti-pan gamma delta + IL-7 was dependent on endogenously produced IL-2. Collectively, these studies suggest that the activation requirements of newborn thymic gamma delta T cells differ markedly from alpha beta T cells in that gamma delta T cells 1) respond to combinations of cytokines in the absence of TCR cross-linking, 2) can respond to TCR cross-linking in the presence of exogenous cytokines, 3) but are unable to activate endogenous cytokine production solely in the presence of TCR cross-linking.

Animals↗

Separation of the polyethylene liner from acetabular cup metal backing. A report of three cases.

In three young patients with cementless Porous Coated Anatomic (PCA) total hip prostheses implanted two to four years previously, the polyethylene liner separated from metal backing. These cups were of the original PCA design, manufactured and packaged as single assembled components, rather than the more recent two-piece components packaged with interchangeable liners separate from the metal backing. Each case of separation was associated with the failure of the thin outer polyethylene rim and central polyethylene peg on the back of the liner that secures it to the metal backing. Cup liners should be securely attached to the metal backing. The possibility of polyethylene failure is considerable when cementless metal-backed acetabular cups are used in active young patients.

Acetabulum↗

Dissection of an inflammatory process induced by CD8+ T cells.

A massive delayed type hypersensitivity (DTH) reaction occurs in the cerebrospinal fluid (CSF) of mice with lymphocytic choriomeningitis (LCM). In this article, Peter Doherty and colleagues analyze this reaction together with the population dynamics of the regional lymph node to give a comprehensive picture of the events underlying this CD8+ T-cell-mediated immunopathological disease. Their findings are of general relevance to the understanding of inflammation.

Animals↗

Phenotypic and functional analysis of the cellular response in regional lymphoid tissue during an acute virus infection.

A phenotypic and functional analysis has been made of the cellular response in regional lymphoid tissue of C57BL/6J mice infected with lymphocytic choriomeningitis virus. Massive recruitment of nondividing cells occurred from 3 days after infection, with total numbers of CD8+ T lymphocytes, B220+ B cells, and Thy-1- B220- null cells being high from day 4 to day 6. In contrast, the peak counts for CD4+ T cells were recorded on day 4 and declined dramatically thereafter. Enhanced expression of IL-2R and Ly-24, both of which can be regarded as T cell activation markers, was found for both the CD4+ and the CD8+ subsets, being most prominent for the CD8+ T cells on day 6. Evidence of T cell proliferation was not recognized until days 5 and 6, coincident with enhanced responsiveness of the lymphocytes to rIL-2 and the development of virus-specific cytotoxic activity. Elimination of the CD4+ T cells by treatment of mice with mAb did not modify either the pathogenesis of lymphocytic choriomeningitis, or the expression of activation markers on the CD8+ T cells which are known to be the key effectors in this disease. Thus, the pattern of responsiveness for the CD8+ population is of recruitment to the lymph node, progressive increase in the expression of activation markers and enhanced sensitivity to rIL-2, with late proliferation and generation of cytotoxic activity. This model provides a system for the rigorous in vivo analysis of parameters influencing lymphocyte differentiation and activation in a virus infection.

Animals↗

Mouse strain variation in Ly-24 (Pgp-1) expression by peripheral T cells and thymocytes: implications for T cell differentiation.

The cell surface glycoprotein Ly-24 has been proposed as a useful marker for the identification of in vivo-primed T cells. Analysis of Ly-24 surface expression by T cells from different mouse strains has shown variation in Ly-24 expression that is not H-2 linked; however, mice of the Ly-24.1 allele (e.g. BALB/c) express relatively high amounts, whereas Ly-24.2 strains (e.g. C57BL/6) are low expressors. In BALB/c (Ly-24 high) and C57BL/6 (Ly-24 low) mice, Ly-24 was expressed by both CD4- CD8+ and CD4+ CD8- subpopulations of single-positive T cells and thymocytes Among CD4- CD8- thymocytes, the overall expression of Ly-24 was similar in both mouse strains. Analysis of CD4+ and CD8+ single-positive thymocytes from newborn and adult BALB/c mice showed that the neonatal population contained fewer Ly-24+ cells. However, using the cell surface markers J11d and CD3, neonatal single-positive thymocytes were found to contain larger numbers of cells with the Ly-24-J11d+CD3 low to negative phenotype. Taken together, these results show that in BALB/c (Ly-24 high) mice, as soon as functional mature phenotype (CD3+) CD4+ and CD8+ single-positive thymocytes are generated, they already express Ly-24. These data cast doubt on the usefulness of Ly-24 expression as a universal marker of in vivo-primed T cells and suggest that in BALB/c mice thymus migrants may well be Ly-24+. Expression of Ly-24 by thymocytes is discussed in the context of current models of intrathymic T cell differentiation.

Aging↗

Persistence of the irradiated host component in thymocyte populations from bone marrow radiation chimeras infected with lymphocytic choriomeningitis virus.

The thymus of chimeras made using T cell-depleted donor bone marrow from Thy1.1+ mice and 950 rad Thy 1.2+ recipients is dominated initially by cells expressing the Thy 1.2+ phenotype of the irradiated host. The thymocyte population recovered at 2 weeks after reconstitution comprises 80% Thy 1.2+ cells (host), the remainder being Thy 1.1+ (donor). This situation is normally reversed within a further week, with the host Ty 1.2+ (donor). This situation is normally reversed within a further week, with the host Thy 1.2+ thymocytes being present at a frequency of less than 5% from Week 4. Infection with lymphocytic choriomeningitis virus (LCMV) at 1 week after reconstitution with bone marrow causes a profound and persistent drop in the total number of thymocytes. The decline is equivalent for all categories of donor-derived thymocytes defined by two-color flow microfluorometric analysis for CD4 and CD8. However, there is a partial compensation by the retention of cells originating from the Thy 1.2+ host, which constitute 30-40% of the total thymocyte pool as late as 8 weeks after administration of bone marrow in the LCMV-infected chimeras. These radiation-resistant precursors give rise to CD4-8-, CD4-8+, CD4+8-, and CD4+8+ thymocytes, with the latter category being present at increased frequency. The potential skewing of the mature T cell repertoire as a consequence of persistent virus infection is discussed.

Animals↗

Virus-specific memory T cells are Pgp-1+ and can be selectively activated with phorbol ester and calcium ionophore.

Memory lymphocytic choriomeningitis virus (LCMV)-immune cytotoxic T-lymphocyte precursors (CTLp) can be stimulated to proliferate and to mediate specific cytotoxic activity following incubation with phorbol myristate acetate (PMA), calcium ionophore (CaI), and interleukin 2 (IL-2). This protocol can be used to selectively induced virus-specific CTL activity under both bulk culture and limiting dilution conditions, in the absence of added antigen. There is no concurrent stimulation of alloreactive CTLp. Proliferation of the effector Lyt-2+ population in medium containing PMA and CaI requires L3T4+ cells, which can be replaced by adding IL-2, and the development of cytotoxicity is totally IL-2 dependent. The LCMV-specific memory T cells are also characterized by the expression of the Pgp-1 (Ly24) glycoprotein. The availability of this marker, together with the capacity to selectively stimulate primed CTLp in the absence of antigen, should greatly facilitate the analysis of T-cell memory in virus infections.

Animals↗

Mandibular fractures in association with chin trauma in pediatric patients.

The combination of chin trauma and bleeding from the ear should alert the physician to the possibility of a mandibular fracture. Not all hemotympanums represent basilar skull fractures, especially when they occur in association with chin trauma. Diagnosis of mandibular condylar fractures or temporomandibular joint disruptions can be very difficult. A high index of suspicion and a proper choice of imaging modalities are necessary to ensure a timely diagnosis.

Accidental Falls↗

Phenotypic analysis of the inflammatory exudate in murine lymphocytic choriomeningitis.

The massive inflammation of the cerebrospinal fluid (CSF) which occurs in adult mice injected with lymphocytic choriomeningitis virus (LCMV) has been analyzed by flow microfluorometry (FMF). The great majority of the T cells detected by direct examination of freshly obtained CSF were found to be Lyt-2+, with an almost total absence of L3T4+ lymphocytes. The Lyt-2/L3T4 ratio of lymphocytes in blood was within normal limits. Predominance of the Lyt-2+ subset was confirmed by culturing the CSF cells after mitogenic stimulation. In addition, the T lymphocytes in CSF of cyclophosphamide-suppressed, virus-infected recipients that had been injected 4 d previously with LCMV-immune spleen cells were almost entirely donor Lyt-2+ cells, while the nonlymphoid elements were exclusively of host origin. However this pattern of donor and host T cell distribution was reversed when the LCMV-infected recipients were not immunosuppressed. The frequency of LCMV-specific CTL precursors in CSF taken immediately before the development of symptoms was as low as 1:3,000 cells. Thus most of the T lymphocytes extravasating into the CSF of mice with LCM are passive participants recruited as a consequence of the function of relatively few LCMV-specific effector T cells. The dominance of the Lyt-2+ T cell subset in the CSF of mice with LCM is intriguing.

Animals↗

Expression of Pgp-1 (or Ly24) by subpopulations of mouse thymocytes and activated peripheral T lymphocytes.

The expression of Pgp-1 (Ly24) by subpopulations of thymocytes was investigated and a subpopulation of Lyt-2-/L3T4-/J11d- thymocytes was identified which contained significant numbers (80%) of Pgp-1+ cells. Among freshly isolated lymph node T cells but not cortisone-resistant thymocytes, Pgp-1 expression was heterogeneous. Stimulation of T lymphocytes with either concanavalin A or the combination of phorbol myristate acetate plus calcium ionophore resulted in increased Pgp-1 expression which was found to be regulated independently of DNA synthesis and interleukin 2 receptor expression. T cells in the cerebrospinal fluid exudate of mice infected with lymphocytic choriomeningitis virus were also found to be Pgp-1+.

Animals↗

Phenotypic properties, interleukin 2 production, and developmental origin of a "mature" subpopulation of Lyt-2- L3T4- mouse thymocytes.

Two-color flow microfluorometry using monoclonal antibodies to cell surface determinants has shown that a subpopulation of mouse Lyt-2- L3T4- thymocytes, comprising 18% of Lyt-2- L3T4- cells in adult C57BL/6 mice, appears in the thymus late during fetal development. These Lyt-2- L3T4- cells are characterized by lack of expression of determinants recognized by monoclonal antibody J11d, a phenotype characteristic of more "mature" functional T cells. This J11d- subpopulation of Lyt-2- L3T4- thymocytes has now been shown to produce significant quantities of interleukin 2 following mitogen stimulation and to express T-cell receptor molecules recognized by monoclonal antibodies KJ-16 and F23.1. Furthermore, culturing of fetal thymus lobes has shown that precursors of this subpopulation of Lyt-2- L3T4- thymocytes are already present in thymus at 14 days of embryonic development and are thus derived from an intrathymic precursor cell. So, within the mouse thymus, phenotypic changes and acquisition of mature T-cell characteristics occur within a subpopulation of cells originally thought of as exclusively "immature."

Age Factors↗

Cefazolin-induced pseudomembranous colitis resulting in perforation of the sigmoid colon.

The seventh case of probable cefazolin-induced pseudomembranous colitis is reported. Perforation of the colon necessitated sigmoid resection. The postoperative course was protracted, and illustrates the difficulty of managing advanced pseudomembranous colitis when the oral route of antibiotic administration is not available. Although rare, pseudomembranous colitis related to cefazolin administration is a potentially fatal complication. The routine use of prophylactic antibiotics must be weighed against this possibility.

Aged↗

Acquired lobar emphysema in premature infants with bronchopulmonary dysplasia: an iatrogenic disease?

Five premature infants in whom bronchopulmonary dysplasia developed following prolonged neonatal respiratory support are presented. In all five patients, right middle and/or lower lobe emphysema related to focal obstructing endobronchial masses of granulation tissue subsequently developed. It is speculated that the granulation tissue formed in response to the repeated mechanical trauma of endotracheal tube suctioning.

Female↗