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Biomedical subjects

K Fredens

Publications and source records attributed to K Fredens.

At least 19 recordsLinked to original sources
PubMed1998

Eosinophil activation in ulcerative colitis: studies on mucosal release and localization of eosinophil granule constituents.

Activation of eosinophil granulocytes (eosinophils) seems to contribute to the pathophysiology of several inflammatory conditions. This process was evaluated in 18 patients with ulcerative colitis and in 18 healthy controls using intraluminal segmental perfusion of the sigmoid colon and rectum and immunoanalysis for eosinophil cationic protein (ECP) in the perfusate. Immunohistochemistry for eosinophils and neutrophils was made in simultaneously taken biopsies and in biopsies from surgical specimens taken from additional 10 patients. The mucosal release of ECP was increased severalfold in patients with UC. The bowel biopsies demonstrated a lamina propria infiltrated with eosinophils. The degree of eosinophil activation/degranulation was related to the intensity of the inflammatory reaction. Activated eosinophils and extracellular deposits of ECP were, in particular, seen in crypt abscesses and in areas with damaged surface epithelium. Since ECP is highly cytotoxic, its release at the site of inflammatory bowel lesions might reflect a potential pathophysiological mechanism.

Adult↗
PubMed1997

Eosinophil cationic protein in mucosal biopsies from patients with allergy and otitis media with effusion.

Nine patients with persistent middle ear effusion and allergy confirmed by skin testing were evaluated for eosinophils by histochemical staining of middle ear mucosal biopsy specimens for eosinophil cationic protein. The study was designed to determine whether eosinophils were present in the middle ear mucosa of these patients and whether the elevated levels of eosinophil cationic protein reported in effusion from patients with chronic otitis media with effusion and allergy might originate within the mucosa itself. Seven of nine patients with otitis media with effusion had eosinophil cationic protein containing eosinophils (12 to 15 per high-power field) and degranulated eosinophil cationic protein material in the stroma of their mucosal biopsy specimens. Positive and negative biopsy findings correlated directly with respective high and low effusion levels of eosinophil cationic protein (p = 0.03), reflecting an intrinsic immune-mediated process occurring within the middle ear mucosa.

Biopsy↗
PubMed1997

Eosinophils in human cervical ripening.

OBJECTIVE: Cervical ripening has many similarities to an inflammatory reaction. Eosinophil granulocytes are involved in several inflammatory responses. The objective was to investigate the presence of eosinophils in human cervix uteri during different conditions. STUDY DESIGN: Cervical biopsies were obtained from non-pregnant (n = 6), women in early pregnancy (n = 11) and from three groups of women at term: spontaneous vaginal deliveries (n = 5); vaginal deliveries after pretreatment with Prostaglandin E2 (n = 7); and from women who underwent planned Caesarean section (n = 7). Immunohistochemical staining for eosinophil granulocytes (ECP, EG2) were performed. The biopsies were analysed blinded. RESULTS: Eosinophils showing degranulation in the tissue were found in all specimens from vaginal deliveries. No eosinophils, or very few were seen in the biopsies from non-pregnant, early pregnant women or planned caesarean section. Prostaglandin treatment had no effect on the results. CONCLUSION: Eosinophils participate in cervical ripening at term in women, and seem to arise mainly after labour.

Blood Proteins↗
PubMed1995

The influence of small changes in the gravitational field on the weight regulation in female Wistar rats.

OBJECTIVE: To determine effect of small gravitational changes on weight regulation in female Wistar rats. METHOD AND RESULTS: Rats submitted to moderate increases in the gravitational field will lose weight. We increased the g force in steps between 1 and 2.5g and found an exponential correlation between weight loss and the gravitational field. The weight loss was reversible upon return to normal g force. In adult fully grown rats we found a marked 'overshooting' upon return to 1g force after a stay at 2g for 5 weeks. CONCLUSION: A hypothesis is proposed suggesting that the weight loss and regain represent the effect of regulatory mechanisms on the appetite control presumably mediated via impulses from the proprioceptive nerves in the extremities.

Animals↗
PubMed1994

Role of eosinophilic granulocytes in women with infertility and pelvic adhesions.

Increased numbers of eosinophilic granulocytes and eosinophil degranulation have been observed in various inflammatory conditions. Biopsies from the fallopian tubes of 28 patients were examined for the content of eosinophilic granulocytes. Peritoneal fluids (PF) from 89 patients were analyzed for the concentrations of eosinophilic granulocytes and the granule protein eosinophil cationic protein (ECP). The ECP levels in the PF were substantially elevated during genital inflammation (P < 0.001). Furthermore, one week after laparotomy for adhesiolysis there were both increased PF-ECP levels (P < 0.01) and raised concentrations of eosinophilic granulocytes (P < 0.001) when compared to the reference group. Staining of the biopsies with monoclonal antibodies revealed an increased total number as well as a number of activated eosinophilic granulocytes in specimens from adhesions and sactosalpinx compared to specimens from normal fimbriae. The findings indicate that eosinophilic granulocytes may have a possible role in the fibrotic process of pelvic adhesion disease.

Adult↗
PubMed1992

Activated astrocytes of the mouse hippocampus contain high levels of NADPH-diaphorase.

NADPH-Diaphorase has recently been shown to be identical to nitric oxide synthase in brain neurones. In the intact brain, NADPH-diaphorase is only present in selected populations of neurones and is not detectable in glia. However following a lesion in the mouse retrosplenial cortex, activated astrocytes display intense NADPH-diaphorase activity throughout their cytoplasm. After a control saline injection, NADPH-diaphorase-positive activated glia are only observed in damaged tissue immediately surrounding the injection site, but when kainic acid is injected unilaterally, activated astrocytes occur in the hippocampal formation bilaterally. This indicates that astrocytes activated by intense neuronal activity, as well as by direct mechanical damage, express high levels of NADPH-diaphorase.

Animals↗
PubMed1991

Eosinophil activation in systemic sclerosis.

Circulating levels of eosinophil cationic protein (ECP) were increased 4-fold in patients with systemic sclerosis (SSc) compared with those in healthy control subjects. There was no correlation between the ECP concentrations and laboratory indices of inflammatory activity or visceral involvement. Mean ECP levels were higher in patients with a history of occupational exposure to silica, even though patients who had no such history also had ECP levels higher than normal. The patients had increased bronchoalveolar levels of ECP, which correlated with impaired lung functioning. Skin infiltration with activated eosinophils and extracellular deposits of ECP were present in skin biopsy samples from the SSc patients. We conclude that eosinophil activation is part of the inflammatory process in SSc.

Adult↗
PubMed1991

In vitro studies of the interaction between heparin and eosinophil cationic protein.

Eosinophil cationic protein (ECP) is a protein specific to the granules of human eosinophil granulocytes, ECP is highly cationic and may damage tissue if not inactivated. Heparin is a highly anionic substance present in mast cells and basophil granulocytes. The present in vitro study shows that ECP can inactivate the anticoagulant activity of heparin probably by the formation of a complex between the two molecules. This function may be of importance for the microenvironment of allergic diseases where secretion of heparin may promote penetration of mast cell products through tissues. Also this may constitute one mechanism whereby the cytotoxic action of ECP is neutralized.

Blood Coagulation↗
PubMed1991

Deposition of eosinophil cationic protein in vascular lesions in temporal arteritis.

The possible role of the eosinophil and its cytotoxic granule proteins in the vascular lesions seen in temporal arteritis was elucidated. Sixteen sections of biopsy specimens from arteria temporalis showing giant cell arteritis were stained for eosinophil cationic protein (ECP) by polyclonal antibodies and the immunoperoxidase method. Activated eosinophils were identified by monoclonal antibodies linked to alkaline phosphatase. Activated eosinophils and secreted ECP were seen in all layers of the inflamed vessels and were most evident in necrotic lesions and thrombi. Only a small number of granulocytes seen in the adventitia were immunoreactive for cathepsin G, and no extracellular deposits of this neutrophil granule protein were seen. A few immunoreactive eosinophils were found in the adventitia in two of five negative temporal artery biopsy specimens from patients with polymyalgia rheumatica. All eight coronary artery biopsy specimens with atherosclerotic lesions showed no activated eosinophils or secreted ECP. These findings indicate that eosinophils are involved in the vascular lesion in temporal arteritis and suggest that cytotoxic eosinophil granule proteins may contribute to the necrotic lesions and the development of thrombi.

Aged↗
PubMed1991

Activated eosinophil infiltration and deposits of eosinophil cationic protein in renal allograft rejection.

Eosinophil involvement in renal allograft rejection was elucidated with immunocytochemical techniques. Sections of renal biopsies were stained for immunoreactive eosinophils and extracellular deposits of eosinophil cationic protein (ECP). Activated eosinophils were identified by means of alkaline-phosphatase-linked monoclonal antibodies. In biopsies from patients with acute rejection of the interstitial type, a varying degree of eosinophil infiltration in the interstitium was seen. Minor extracellular deposits of ECP were present in areas with activated eosinophils. In acute vascular rejection, dense infiltration of activated eosinophils and secreted ECP were found in infarcted areas and in arterial walls with necrotic lesions. Dense accumulation of activated eosinophils and extracellular deposits of ECP were also seen in biopsies from non-transplanted patients with necrotizing renal vasculitides. These findings suggest that cytotoxic eosinophil granule proteins are involved in vascular injury in renal graft rejection and in necrotizing renal vasculitides. Eosinophil activation may also have a pathophysiological role in the interstitial lesions in renal graft rejection.

Antibodies, Monoclonal↗
PubMed1990

The eosinophil granulocyte in psoriasis.

The presence of eosinophils and eosinophil cationic protein (ECP) in the involved and non-involved skin in patients with psoriasis was studied using a polyclonal antibody specific for ECP and a monoclonal antibody (EG2) specific for activated eosinophils and secreted ECP. ECP immunoreactive eosinophils were found in all the specimens from involved psoriatic skin. In new lesions in patients with rapidly progressive disease, intense ECP immunoreactivity was detected both intra- and extracellularly, particularly in the upper third of the epidermis and usually in association with granulocytes. In stable or slowly progressive lesions, less ECP was observed. The EG2-immunoreactivity was positive in the same areas. ECP was also determined in suction-blister fluid from lesional and non-involved skin in psoriasis patients and in healthy subjects. The ECP concentration was greatly elevated in the fluid from lesions in patients with more acute and progressive disease.

Adolescent↗
PubMed1989

Relationship of afferent inputs to the lattice of high NADPH-diaphorase activity in the mouse superior colliculus.

In the intermediate gray layer of the superior colliculus there is a lattice of high NADPH-diaphorase activity which represents the terminal distribution of a number of extrinsic afferent systems. These include inputs from the dorsal cholinergic column and cells in the precommissural nucleus and dorsolateral wedge of the central gray substance. Other afferents that terminate in the intermediate gray layer, such as the input from the nucleus of the brachium of the inferior colliculus (BIN), are almost completely segregated from the above inputs and show very little overlap with the NADPH-diaphorase lattice. It is suggested that the input from the precommissural nucleus and central gray substance may have a role in nociception while the input from BIN may provide an important source of auditory information.

Animals↗
PubMed1989

Severe destruction of esophageal nerves in a patient with achalasia secondary to gastric cancer. A possible role of eosinophil neurotoxic proteins.

We present a case of secondary achalasia due to an adenocarcinoma of the stomach with no tumor infiltration of the esophagus. Immunohistochemical staining revealed a massive infiltration of activated eosinophils in the muscularis of the esophagus with secretion of the highly cytotoxic and neurotoxic eosinophil cationic protein (ECP). Immunohistochemical staining for the neuropeptides VIP and substance P, as well as the histochemical demonstration of AChE, revealed a nearly total absence of all three neurotransmitters/modulators compared to control. The hypothesis is advanced that eosinophil neurotoxicity is the cause of secondary achalasia.

Adenocarcinoma↗
PubMed1989

Eosinophil infiltration in primary esophageal achalasia. A possible pathogenic role.

Smooth-muscle specimens from the lower esophagus of nine patients operated on for esophageal achalasia were examined with routine hematoxylin-eosin staining. This procedure revealed only a few eosinophils in or between the external smooth-muscle layers. Using specific immunohistochemical methods for the detection of the eosinophil cationic protein (ECP), however, varying degrees of eosinophil infiltration and extracellular deposit of ECP were disclosed in the achalasia specimens. The ECP also reacted with the monoclonal antibody, EG2, indicating secretion of the cytotoxic ECP. Few or no eosinophils were seen in the muscularis externa in specimens from six control patients without esophageal disease. In two controls many eosinophils were observed in the muscularis externa. However, no extracellular ECP was detected and very few eosinophils reacted with the monoclonal antibody (EG2), suggesting that these eosinophils were not activated. Depletion or total absence of peptidergic innervation was seen in all achalasia specimens but not in controls. Since the eosinophil cationic protein (ECP), in its activated form, is cytotoxic, we propose a pathogenic role of the eosinophil infiltration in achalasia.

Adult↗
PubMed1989

Neutrophil and eosinophil involvement of the small bowel in patients with celiac disease and Crohn's disease: studies on the secretion rate and immunohistochemical localization of granulocyte granule constituents.

PURPOSE: The concentrations of myeloperoxidase (MPO), a neutrophil granule constituent, and eosinophil cationic protein (ECP), a specific eosinophil granule protein, were measured in jejunal perfusion fluid in an attempt to elucidate the neutrophil and eosinophil involvement of the small bowel in health and disease. PATIENTS AND METHODS: The control group consisted of 14 males and two females. Ten patients (seven males and three females) with Crohn's disease and seven patients (two males and five females) with celiac disease were also studied; in addition, one patient with relapsing giardiasis, one patient with giardiasis and complete absence of plasma cells in small intestinal lamina propria, and one patient with selective IgA deficiency and no IgA plasma cells in duodeno-jejunal lamina propria were evaluated. Segmental perfusion of the jejunum was performed according to a previously described method. MPO and ECP were measured by radioimmunoassays. RESULTS: In healthy control subjects, the concentrations of both granule proteins were in a narrow range and much higher than would have been anticipated from passive leakage from circulating blood. In patients with celiac disease, the perfusion fluid concentrations of MPO and ECP were on average 3.5 and eight times, respectively, higher than the values seen in the controls. The jejunal segment perfused in patients with Crohn's disease was endoscopically and histologically normal. The perfusion fluid concentrations of MPO and ECP were increased 3.5 and two times, respectively, compared with that in the control subjects. Both patient groups and the control group had similar perfusion fluid concentrations of albumin. Data on MPO and ECP expressed as jejunal secretion rates gave the same differences between patients and controls as just described for the jejunal fluid concentrations. Immunohistochemical studies of jejunal biopsy specimens from another group of patients with celiac disease demonstrated a prominent extracellular deposit of ECP in the lamina propria of the atrophic intestinal mucosa, whereas the release of neutrophil constituents (cathepsin G, MPO) was scarce. In Crohn's disease, an extracellular degranulation of ECP and, to a lesser extent, of cathepsin G was observed in relation to ulcerations only. CONCLUSION: Data obtained indicate that the local release of neutrophil and eosinophil granule components is enhanced in the jejunal tissue from patients with celiac sprue and Crohn's disease. The prominent extracellular deposit of eosinophil granule constituents with cytotoxic properties at the site of inflammatory intestinal lesions in celiac sprue might reflect a pathophysiologic mechanism.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗
PubMed1988

Origin of high acetylcholinesterase activity in the mouse superior colliculus.

The acetylcholinesterase activity in the colliculus mainly occurs in two layers and is arranged as a lattice in the intermediate grey layer and as a continuous sheet in the superficial grey layer. Undercutting lesions abolish the lattice in the intermediate grey layer but leave the superficial sheet of activity intact. By contrast the injection of kainic acid into the colliculus leaves the intermediate layer lattice intact while causing a local reduction in the superficial layer. Injections of the retrograde tracer Fluoro-Gold into the colliculus labels cells in the pedunculopontine and laterodorsal tegmental nuclei that contains acetylcholinesterase. Cells in the parabigeminal nucleus are also labelled but these cells contain low levels of cholinesterase. Thus, it is concluded that the lattice in the intermediate layers is mainly dependent on afferents from the laterodorsal tegmental and pedunculopontine nuclei while the sheet in the superficial layers is mainly dependent on intrinsic cells.

Acetylcholinesterase↗