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Biomedical subjects

T Koch

Publications and source records attributed to T Koch.

At least 163 records · Page 9Linked to original sources
PubMed1997

Yolk sac-derived murine macrophage cell line has a counterpart during ES cell differentiation.

Macrophages are phagocytic hematopoietic cells involved in several immune processes, but they are also present early in mammalian development and may participate in embryonic tissue remodeling. We have isolated and characterized a cell line, Py-YSA, from the mouse yolk sac. Py-YSA cells have several functional properties of macrophages, including uptake of acetylated low density lipoprotein and phagocytic capability. They express the murine macrophage markers F4/80 and Mac-1, and they express RNA for the c-fms receptor. Their expansion in culture requires fibroblast conditioned medium or exogenous monocyte-colony stimulating factor. Murine ES (embryonic stem) cell cultures that undergo in vitro differentiation recapitulate yolk sac development, and during this process cells arise that express both Mac-1 and F4/80 and morphologically resemble the Py-YSA cells. The kinetics and distribution pattern of the Mac-1+ cells during a time course of ES cell differentiation suggest that they originate in the blood islands, and that they subsequently leave the blood islands and disperse to tissue sites. Both F4/80 and Mac-1 are first expressed in primary cultures from day 9.5 yolk sacs. The Py-YSA cultured cells thus resemble embryonic tissue macrophages by several criteria, and they share a marker profile with a cell type found in yolk sacs and differentiating ES cells. Py-YSA cells will be a useful reagent for further understanding the role of embryonic tissue macrophages in development.

3T3 Cells↗
PubMed1997

Expression of the immunoglobulin superfamily cell adhesion molecule F3 by oligodendrocyte-lineage cells.

We have analysed the expression of glycosylphosphatidylinositol (GPI)-anchored proteins by oligodendrocyte-lineage cells. Biosynthetic labeling of mouse oligodendroglial primary cultures and an oligodendroglial precursor cell line demonstrated that these cells synthesise a variety of different GPI-anchored proteins. GPI-anchored proteins were isolated as a bulk preparation from the precursor cell line, and the individual proteins separated by 2D gel electrophoresis and analysed by microsequencing after tryptic digestion of the separated components. One of the most prominent GPI-anchored proteins synthesised by the cell line was identified as the cell adhesion molecule F3, previously thought to be exclusively expressed by neurons. Western blotting and immunoprecipitation with several polyclonal sera confirmed the expression of F3 by oligodendrocyte-lineage cells and demonstrated the presence of F3 in myelin. Double staining with a panel of oligodendrocyte-specific antibodies and anti-F3 antibodies of cerebellar cultures, as well as oligodendrocytes isolated by panning, showed a colocalization of F3 with oligodendrocyte markers. Oligodendrocyte F3 is shown to be susceptible to phosphatidylinositol-phospholipase C (PI-PLC) cleavage, similar to neuronal F3. Northern blots demonstrated that the oligodendroglial F3 mRNA is the same size as the neuronal message; however, no F3 mRNA could be detected in cortical astrocytes and an astrocytic cell line. Thus, in addition to the expression by neurons, the cell-type specificity of F3 expression must be extended to oligodendroglial cells, underscoring the importance of this Ig superfamily member in the nervous system.

Animals↗
PubMed1997

Effects of bradykinin, histamine and serotonin on pulmonary vascular resistance and permeability.

The effects of bradykinin, histamine and serotonin on vascular resistance and microvascular permeability were investigated in isolated cell-free perfused rabbit lungs. The capillary filtration coefficient was determined from the slope of lung weight changes over periods of venous pressure elevation before application of bradykinin (n = 6), histamine (n = 6) and serotonin (n = 6), and 5, 20 and 50 min afterwards. To prevent rapid inactivation of bradykinin by the angiotensin-converting enzyme in the pulmonary circulation, the bradykinin effects were additionally studied in the presence of the angiotensin-converting enzyme inhibitor captopril (n = 6). Bolus application of each substance resulted in a short-lasting increase in the pulmonary vascular resistance (3.7-9.1 mmHg). Which was most pronounced in the bradykinin+captopril group. The capillary filtration coefficient was significantly increased after histamine application, and to an even greater extent after serotonin application, whereas bradykinin on its own, as well as bradykinin given in the presence of captopril, had no measurable influence on capillary filtration in the lung. As a result of the bradykinin challenge, there was an immediate massive generation of prostacyclin, which could not be further augmented by a application. Histamine injection entailed a delayed onset of prostacyclin generation after the second stimulation, whereas no prostacyclin increase was measured in the serotonin-treated lungs. Thromboxane A2 generation was exclusively observed after the first serotonin application. The data exemplify different pathophysiological characteristics of bradykinin, histamine and serotonin on lung barrier function. Histamine and serotonin induce oedema formation by enhancing microvascular permeability, whereas bradykinin does not.

6-Ketoprostaglandin F1 alpha↗
PubMed1997

Engagement and detachment: understanding patients' experiences with nursing.

This study aimed to understand what post-operative patients perceived was important about the nursing care they had experienced. The participants were nine women recovering from total hip replacement surgery which had been performed in a large public, acute care hospital in south Australia. Participants volunteered to be involved in the study and were interviewed pre- and post-operatively and interviews continued in their home environment following discharge. The study took place during 1995 within a 10-month time frame. Methodological guidance was sought from the phenomenology literature, with the ideas from Husserl and Heideggar providing shape for the interpretive framework. The analysis of data utilized Colaizzi's (1978) seven procedural steps. For the purposes of this paper the authors have selected to focus only on the findings of this study. Two major themes emerged from the conversations with women. Patients described nurses as being engaged or detached with their nursing care. These themes will be explicated in this paper. In the light of these dominant themes the nursing literature around engagement and detachment are examined. The implications for nursing practice are discussed.

Attitude to Health↗
PubMed1997

Women's experiences of non-invasive breast cancer: literature review and study report.

A review of the post-1990 literature on breast cancer has identified a large body of psychosocial research focusing on coping styles, quality of life and women's participation in choice of treatment. However, numerous methodological problems were found, including a variety of different diagnoses included in samples both within studies and between studies, making comparisons difficult. In particular, no article was traced which focused on non-invasive breast cancer, or ductal carcinoma in situ (DCIS). Therefore a small exploratory study was conducted using qualitative methods to explore women's experience of DCIS, in an attempt to begin exploration of possible similarities or differences in the way women experience invasive and non-invasive breast cancer. A convenience sample of 10 women treated at two hospitals in an Australian state capital city was interviewed, and three themes which emerged from these interviews are discussed in this article. These are discovering the problem, reaction to the diagnosis, and information. Most women unexpectedly reacted in a calm and accepting way to receiving the diagnosis of DCIS, and this may be because they had had no signs of disease but been recalled for further tests after routine screening. They felt well and had no cause to assume a poor prognosis. It is possible also that their reactions were affected by a television health education campaign at the time, which gave a very optimistic picture of the benefits of early detection of breast cancer. Information-giving, as reported by the women, seemed deficient. None of them knew that they had had a non-invasive condition, one thought her disease had been benign, and another that hers was "evasive'. Findings are discussed in relation to the literature on information-giving and on the role of the nurse in this area, and suggestions are made for further research to systematically compare women's reactions to having invasive and non-invasive breast cancer in order that nurses may be aware of their possibly different needs and respond to them appropriately.

Adaptation, Psychological↗
PubMed1997

Site mutation in the rat mu-opioid receptor demonstrates the involvement of calcium/calmodulin-dependent protein kinase II in agonist-mediated desensitization.

The rat mu-opioid receptor (rMOR1), expressed in human embryonic kidney 293 (HEK293) cells, shows a desensitization to the inhibitory effect of the mu agonist DAMGO on adenylate cyclase activity within 4 h of DAMGO preincubation. To investigate the role of calcium/calmodulin-dependent protein kinase II (CaM kinase II) on mu-opioid receptor desensitization, we coexpressed rMOR1 and constitutively active CaM kinase II in HEK293 cells. This coexpression led to a faster time course of agonist-induced desensitization of the mu-opioid receptor. The increase of desensitization could not be observed with a mu-opioid receptor mutant (S261A/S266A) that lacks two putative CaM kinase II phosphorylation sites in the third intracellular loop. In addition, injection of CaM kinase II in Xenopus oocytes led only to desensitization of expressed rMOR1, but not of an S261A/S266A receptor mutant. These results suggest that phosphorylation of Ser261 and Ser266 by CaM kinase II is involved in the desensitization of the mu-opioid receptor.

Adenylyl Cyclase Inhibitors↗
PubMed1997

[The significance of endothelin for physiologic and pathophysiologic processes of the lung].

The endothelins (ETs) are a family of three vasoactive peptides (ET-1, ET-2, ET-3) that were first described in 1988. ETs have a wide range of action including vasoconstriction, vasodilatation, bronchoconstriction, and mitogenesis. Two types of ET receptors, classified as ETA and ETB receptors, have been identified in gene technology. Endothelins are produced by endothelial cells, smooth muscle cells, and bronchial epithelial cells. Their vasoactive effects contribute not only to homoeostasis but ETs seem also to be involved in several pulmonary diseases. Elevated ET plasma levels have been found in patients suffering from asthma, pulmonary fibrosis, pulmonary hypertension, and acute lung injury. This review gives a short summary of the actual facts in endothelin research, focussing on the effects of ET-1 in pulmonary circulation.

Animals↗
PubMed1997

[Effects of human i.v. immunoglobulin on bacterial clearance and granulocyte function in endotoxinemia].

PURPOSE: The therapeutic impact of intravenous immunoglobulins (ivIG) in septic patients remains controversial. Until now, the mechanisms of action have not been fully elucidated. Since polymorphonuclear neutrophils (PMN) play a key role in host defence, this study focuses on the effects of ivIG on bacterial clearance and PMN respiratory burst activity during endotoxinaemia. For this purpose, it was investigated whether ivIG improves blood clearance and organ colonisation as well as PMN functions after experimentally induced bacteraemia in rabbits. METHODS: The experiments were performed in 30 anaesthetised rabbits. To determine quantification of bacterial killing in vivo, defined numbers of exogenous Escherichia (E.) coli 1.3 x 10(8) CFU) were injected intravenously in untreated animals (n = 10) or 60 min after infusion of endotoxin (LPS: 40 micrograms/kg/h) in groups without (n = 10), and after pretreatment with ivIG (Sandoglobulin, 0.5 g/kg body weight, n = 10), respectively. Parameters monitored were rates of bacterial elimination from the blood, LPS clearance, arterial pressure, blood gases and white blood cell counts, PMN burst activity was determined using a flow cytometry assay. Samples of liver, kidney, spleen and lung were collected for bacterial counts 180 min following E. coli injection. RESULTS: Compared to controls, endotoxinaemia resulted in a prolonged elimination of the injected E. coli out of the blood associated with a significantly (p < 0.01) higher colonisation of all organs. Pretreatment with ivIG improved LPS clearance and significantly reduced bacterial colonisation of lung and kidney (p < 0.01). This was paralleled by an enhanced PMN respiratory burst activity compared to untreated animals (p < 0.05). CONCLUSION: The reduced bacterial colonisation of lung and kidney in correlation with an increased PMN bactericidal activity in endotoxinaemia suggest an improved granulocyte-dependent bacterial killing due to ivIG application.

Animals↗
PubMed1997

Impaired bacterial clearance after activation of the complement and coagulation systems.

The aim of this study was to investigate the influence of the activation of the complement and coagulation systems on bacterial clearance and killing capacity of the reticuloendothelial system in rabbits. To enable quantification of the clearance process, defined numbers of exogenous Escherichia coli (1.3 x 10(8) colony-forming units) were injected intravenously, after complement activation with inulin-activated rabbit serum (n = 6), after complete defibrination with the snake toxin ancrod (n = 6), and in sham-operated animals (controls, n = 6). During the following 180 min observation period, parameters monitored were arterial pressure, fibrinogen, blood gases, and bacterial counts in blood and tissue samples of liver, kidney, spleen, and lung. Defibrination produced a significant delay in blood clearance (p < .05) compared with controls, coupled with up to four times higher bacterial counts in organ homogenates. Complement activation did not affect bacterial elimination kinetics, but was associated with accumulation of E. coli in lung and kidney (up to 100-fold of control values, p < .001). The impaired bacterial clearance associated with increased organ colonization after activation of the complement and coagulation systems reflect reticuloendothelial system dysfunction, thus pointing toward a weaker resistance against bacterial infection.

Animals↗
PubMed1997

Improvements in automated PNA synthesis using Boc/Z monomers.

An optimized automated PNA synthesis protocol is reported. Under optimal conditions the product yield of a test 17-mer PNA is approximately 90%. The average coupling yield is 99.4%. The synthesis strategy is Boc/Z and the deprotected amine is neutralized in situ. The monomers are added in molar excess to HATU and pre-activated for 60 s before delivery to the resin. The concentration of the activated monomers is 0.08 M during the couplings. Heteroselective solvation provides the highest coupling yields. Acetic anhydride is used as capping reagent followed by a piperidine wash. The protocol has been developed in a 5 mumol scale but is easily scaled up to 10-50 mumol scale syntheses on the automated synthesizer (ABI 433A).

Biopolymers↗
PubMed1997

An attempt to give nursing home residents a voice in the quality improvement process: the challenge of frailty.

Advanced frailty and confusion of many nursing home residents present a particular conundrum to researchers committed to resident participation. While the research is set in Australia, the challenge of frailty is common to researchers working with compromised older persons. This study was conducted in an Australian 32 bed nursing home. As researchers we took on the roles of facilitators and negotiators within a quality improvement process using the approach of fourth generation evaluation. The overall aim of the project was to provide all stakeholders, including residents and their significant others, with a voice in the negotiations and decisions that impact on their lives. The focus of this paper is our attempt to gain the perspective of residents and significant others.

Aged↗
PubMed1996

Lack of cross-tolerance between haloperidol and clozapine towards Fos-protein induction in rat forebrain regions.

We investigated whether the acute effects of haloperidol and clozapine on Fos expression in the rat forebrain are mediated by the same receptors through evaluation of cross-tolerance, particularly in the commonly affected areas. Acutely administered haloperidol (1 mg/kg. i.p.) and clozapine (20 mg/kg, i.p.) induce regionally different (e.g., the striatum, the hypothalamic paraventricular and supraoptic nuclei, and the central amygdala) and overlapping (e.g., the nucleus accumbens and the lateral septum) patterns of Fos-protein distribution in the rat forebrain. After long-term treatment, part of the acute effects of these drugs disappears in most brain areas, except in the lateral septum, the hypothalamic paraventricular and supraoptic nuclei and the amygdala following haloperidol administration. Cross-tolerance between haloperidol and clozapine was determined by administering a challenge dose of the one antipsychotic, following a 21-day pretreatment with the same or the other drug or saline. In none of the investigated brain regions was cross-tolerance towards Fos-protein induction found after haloperidol challenge in the clozapine-treated rats. Conversely, a competitive dose of clozapine in long-term haloperidol-treated rats showed cross-tolerance in the lateral septum, while the common effect of the drugs in both the dorsomedial and the dorsolateral parts of the striatum was very small. These findings indicate that, for the major part, the responses to haloperidol and clozapine are mediated by different receptors, even in brain areas that are affected by both drugs.

Animals↗
PubMed1996

A general assay for antibody catalysis using acridone as a fluorescent tag.

A simple and highly sensitive catalysis assay is demonstrated based on analyzing reactions with acridonetagged compounds by thin-layer chromatography. As little as 1 pmol of product is readily visualized by its blue fluorescence under UV illumination and identified by its retention factor (Rf). Each assay requires only 10 microliters of solution. The method is reliable, inexpensive, versatile, and immediately applicable in repetitive format for screening catalytic antibody libraries. Three examples are presented: (i) the epoxidation of acridone labeled (S)-citronellol. The pair of stereoisomeric epoxides formed is resolved on the plate, which provides a direct selection method for enantioselective epoxidation catalysts. (ii) Oxidation of acridone-labeled 1-hexanol to 1-hexanal. The activity of horse liver alcohol dehydrogenase is detected. (iii) Indirect product labeling of released aldehyde groups by hydrazone formation with an acridone-labeled hydrazide. Activity of catalytic antibodies for hydrolysis of enol ethers is detected.

Acridines↗
PubMed1996

Normative and prescriptive criteria: the efficacy of organ transplantation allocation protocols.

Normative criteria adopted to assure just, equitable, and efficient allocation of donor organs to potential recipients has been widely praised as a model for the allocation of scarce medical resources. Because the organ transplantation program relies upon voluntary participation by potential donors, all such programs necessarily rely upon public confidence in allocation decision making protocols. Several well publicized cases have raised questions in North America about the efficacy of allocation procedures. An analysis of those cases, and the relevant technical literature, suggest consistent structural deficits exist in the organ allocation process as it is applied by many individual transplantation centres. These irregularities are based upon both the failure of rank waiting as a method to guarantee just treatment and a general failure to recognize the extent to which prescriptive criteria--social values--are commonly used to screen potential organ transplant candidates. Resulting idiosyncratic determinations, and a devaluation of rank waiting as a criterion, raise fundamental questions regarding justice, fairness, and equability in the application procedure at large. To correct these structural problems in organ allocation procedures, a multicriterion model defining prescriptive criteria through the Analytic Hierarchy Process (AHP) is proposed.

Consensus↗
PubMed1996

Impairment of bacterial clearance induced by norepinephrine infusion in rabbits.

OBJECTIVE: Purpose of the study was to investigate the potential influence of norepinephrine (NE) on immune functions in terms of systemic and organ-specific bacterial clearance in rabbits. DESIGN: To enable quantification of the clearance process, defined numbers of exogenous Escherichia coli (1.3 x 10(8) CFU) were injected intravenously 60 min after starting the NE infusion at a low dose (1 microgram/kg per min, n = 6), causing an increase (30 mmHg) in mean arterial pressure without affecting the oxygen uptake, and at a higher dose (7.5 micrograms/kg per min, n = 6), resulting in a marked decrease (20%) in oxygen uptake, after infusion of NaCl solution (control, n = 6). In additional experiments (n = 6) NE (1 microgram/kg per min) was tested in endotoxemia induced by simultaneous infusion of endotoxin (40 micrograms/kg per h). Parameters monitored were arterial pressure, oxygen uptake, and rates of bacterial elimination from the blood. At 180 min after E. coli injection, the animals were sacrificed, and tissue samples of liver, kidney, spleen, and lung were collected for bacterial counts. RESULTS: NE infusion resulted in a dose-dependent prolonged elimination of the injected E. coli from the blood and in significantly higher (p < 0.05) numbers of CFU in liver and lung compared to the controls. Significant impairment of bacterial clearance was found after shock-producing endotoxemia, whereas simultaneous infusion of NE and endotoxin caused only a slightly delayed blood clearance of the injected bacteria. CONCLUSION: NE dose dependently affected bacterial clearance, which might be due to ischemia-derived hypoxic impairment of the phagocytosis and lysis function of the reticuloendothelial system, whereas NE improved elimination of bacteria in a state of endotoxic shock.

Animals↗
PubMed1996

Vitamin B6 and hemodialysis: the impact of high-flux/high-efficiency dialysis and review of the literature.

High-flux/high-efficiency (HF/HE) dialysis is associated with improved clearance for larger molecules, which include a wide variety of middle molecules and water-soluble vitamins. Our study attempted to measure in vivo clearances of serum pyridoxal-5'-phosphate (PLP), the active metabolite of vitamin B6, on standard cuprophan versus cellulose triacetate HF/HE dialysis for patients maintained on 10 mg daily pyridoxine supplements. A longitudinal evaluation of PLP after 3 months on HF/HE dialysis was performed simultaneously. The average in vivo PLP clearance for six patients on standard hemodialysis increased by more than 50%, from 86 +/- 61.7 mL/min using a cuprophan membrane to 173 +/- 90.2 mL/min using a cellulose triacetate dialyzer, at average blood flows of 375 mL/min (P < 0.05). Levels of PLP decreased from a baseline of 50 +/- 13.8 ng/mL to 24 +/- 9.7 ng/mL (P < 0.05) after 3 months of HF/HE treatments; the levels returned to 45 +/- 6.4 ng/mL on resumption of standard dialysis treatments. Although not achieving statistical significance, the average hematocrit increased from 31.2% +/- 1.66% to 32.7% +/- 1.24% while on HF/HE dialysis without an increase in erythropoietin requirements. We conclude that HF/HE dialysis treatments can have a dramatic impact on vitamin B6 homeostasis. Further investigation to evaluate the effects of different membranes and reprocessing should be performed on more heterogeneous patient populations in whom compliance problems with diet and vitamin supplementation may exist. The increased clearance of vitamin B6 may have significantly more detrimental effects in these settings.

Adult↗