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Biomedical subjects

O Johansson

Publications and source records attributed to O Johansson.

At least 127 records · Page 7Linked to original sources

Bubble and membrane oxygenators--comparison of postoperative organ dysfunction with special reference to inflammatory activity.

Bubble and membrane oxygenators (2 types of each) were compared in a randomized study of 96 patients undergoing coronary bypass grafting. Cardiac performance, assessed from postoperative need of inotropic support, was significantly better in the membrane oxygenator group. After perfusion lasting more than 2 hours, respiratory function, measured as alveolar-arterial oxygen pressure gradient, was less compromised in that group and renal function, quantified as postoperative rise of serum creatinine was less disturbed. Cerebral function, studied in terms of psychometric test results and concentration of adenylate kinase in cerebrospinal fluid, did not differ between the bubble and membrane oxygenator groups. In investigations concerning changes in inflammatory activity during bypass, complement activation could not be related to the mentioned clinical parameters. Release of the neutrophil granulocyte factors lactoferrin and myeloperoxidase was greater in the bubble oxygenator group and correlated to impaired cardiac and renal performance, but not to pulmonary or cerebral dysfunction.

Adult↗

[Interactions between cytostatic agents and other drugs].

Drug interactions are increasingly common, since the clinical practice is getting more complex with the flood of new drugs. Simultaneously, the increased life expectancy of the population increases the number of individuals likely to receive multiple prescriptions. Cytotoxic drugs generally have a narrow therapeutic index, and are delivered at doses close to toxic levels. Consequently, a slight increase of the biological activity caused by an interaction with other concomitantly administered drugs could be deleterious for the patient. Interactions between drugs can sometimes also be used in a positive way, i.e. to increase the therapeutic ratio. Interactions between different cancer treatment modalities have attracted considerable interest. However, much less interest has been denoted to interactions between anticancer drugs and other pharmaceuticals. The purpose of this review is to summarize data about the interactions between anticancer drugs and other clinically used drugs with regard to effects on tumor and toxicity.

Antineoplastic Agents↗

Intraepidermal neuron-specific enolase (NSE)-immunoreactive nerve fibres: evidence for sprouting in uremic patients on maintenance hemodialysis.

The use of indirect immunohistochemistry in 12 patients on maintenance hemodialysis has shown weak or moderately strong neuron-specific enolase (NSE)-immunoreactive nerve terminals and fibres sprouting throughout the layers of the epidermis. No such terminals or fibres were found in any of 15 controls. There was no difference between uremic patients with pruritus and those without. Furthermore, NSE-positive nerve fibres with a normal appearance were seen in the dermis, at the epidermal-dermal junctional zone and sometimes entering the stratum basale in both patients and controls. The immunoreactive nerves were thin, smooth and, at their terminal fields, varicose. The immunoreactivity seemed to be associated chiefly with sensory nerves. Thus, our results suggest that uremic patients undergoing maintenance hemodialysis develop an abnormal pattern of cutaneous innervation.

Adult↗

Experimental and immunohistochemical studies on the possible role of parathyroid hormone in uraemic pruritus.

Secondary hyperparathyroidism has been suggested as a cause of itching in chronic renal failure. The aim of the present study was to evaluate the possible role of parathyroid hormone (PTH) in pruritus affecting patients undergoing maintenance haemodialysis. In agreement with our previous findings, patients with pruritus had significantly (P less than 0.01) higher serum levels of PTH fragment 53-68 (m-PTH53-68) than patients without pruritus, 47.7 +/- 40.0 and 23.4 +/- 17.1 micrograms l-1 respectively. Serum concentrations of other substances including calcium, phosphate and magnesium did not differ between the two groups of patients. Intradermal injections of human PTH1-34 and PTH44-68 failed to evoke any acute or delayed cutaneous reactions in either patients or controls. Immunohistochemical investigations of skin biopsies from uraemic patients using several different antibodies against PTH were negative. Thus, the present results do not support PTH as a peripheral mediator of uraemic itching.

Adult↗

Immunohistochemical study of neurochemical markers in gingiva obtained from periodontitis-affected sites.

Immunohistochemical methods have been used to study the occurrence of neuronal markers in human gingiva from periodontitis-affected sites. In periodontitis-affected buccal gingiva densely distributed neurofilament (NF)-immunoreactive (IR) fiber bundles were observed in the deeper parts of the propria, while NF-IR single fibers occurred in the superficial propria and occasionally in the buccal epithelium. Periodontitis-affected gingiva obtained from interproximal sites showed only sparsely distributed NF-IR fibers. Single nerve fibers immuno-reactive to the peptides substance P and calcitonin gene-related peptide occurred close to or within the epithelium in both buccal and interproximal gingiva. Around blood vessels neuropeptide Y-, peptide histidine-isoleucine amide- and vasoactive intestinal polypeptide-IR fibers were occasionally observed, while clusters of gamma-melanocyte-stimulating hormone-IR cells were found in the propria, in addition to gamma-melanocyte-stimulating hormone IR nerve fibers. Somatostatin-IR dendritic cells were seen in epithelium and propria of buccal and interproximal gingiva, although a high variability in the number of SOM-IR cells was observed. All neuronal markers studied showed a similar distribution in material obtained from young patients with clinically healthy gingivae, although the number of NF-IR fibers in the propria in these subjects was lower. The results demonstrate that in gingiva obtained from periodontitis-affected sites several different biologically active peptides occur in both nerve fibers and cells. At least some of these substances could possible play a role in the inflammatory process. However, since clinically normal gingiva was shown to contain nerve fibers and cells expressing immunoreactivity to the substances studied, no unique periodontitis-induced expression of the neuronal markers studied was found. Thus, any alteration of these substances during the periodontitis process remains to be elucidated.

Adolescent↗

Effect of the neuropeptides beta-MSH, neurotensin, NPY, PHI, somatostatin and substance P on proliferation of lymphocytes in vitro.

Various neuropeptides were tested in a wide dose range for an effect on lymphocyte-proliferation. The response of spleen cells to the mitogen phytohaemagglutinin (PHA) was stimulated by somatostatin in doses ranging from 10(-6) to 10(-18) M. The effect of somatostatin was only seen when the peptide was added at the start of incubation, indicating an effect on the inductive phase of mitogen stimulation. Weak stimulative effects were also seen of somatostatin (10(-6) M) on spontaneous proliferation of thymocytes and of beta-MSH on PHA-treated thymocytes and PHA-treated spleen cells when the peptide was added after 24 h of culture.

Animals↗

Immunohistochemical studies of the neurochemical markers, CGRP, enkephalin, galanin, gamma-MSH, NPY, PHI, proctolin, PTH, somatostatin, SP, VIP, tyrosine hydroxylase and neurofilament in nerves and cells of the human attached gingiva.

Punch biopsies were obtained from the buccal gingiva of the lower third molars. Thin nerve fibres, immunoreactive for calcitonin gene-related peptide (CGRP) or substance P (SP), with possible sensory function, were found in the propria often close to the epithelium, sometimes even penetrating into the basal layers. gamma-Melanocyte stimulating hormone (gamma-MSH)-like immunoreactivity was found in sparsely distributed single cells (except in one specimen containing a dense infiltration), resembling neutrophilic granulocytes of the propria. gamma-MSH was present in several single smooth axons and in thick axon bundles of the propria. Surrounding the blood vessels, neuropeptide Y (NPY), tyrosine hydroxylase (TH), vasoactive intestinal polypeptide (VIP) and peptide histidine isoleucine amide (PHI) immunoreactive nerve fibres were observed. NPY and TH-positive fibres probably represent sympathetic nerve terminals and VIP/PHI-immunoreactive ones may have a parasympathetic function. Papillae of the propria contained VIP-positive fibres not obviously related to blood vessels. The distribution in papillae of PHI-like immunoreactivity was similar but the PHI-positive reaction was also present in a few cells of the propria, especially near blood vessels. Somatostatin (SOM)-positive reaction occurred in a few dendritic-type cells near or in the epithelium and single nerve fibres close to the epithelium. Several thick axon bundles of the propria contained neurofilament (NF)-immunoreactive material. Some thin NF-fibres were found in the papillae and some seemed to penetrate into the epithelium. No galanin, methionine-enkephalin, parathyroid hormone or proctolin immunoreactive material was found. The rather rich content of several neuropeptides in human attached gingiva, as well as other neurochemical markers, is probably associated with sensory and autonomic functions.

Adult↗

Immunohistochemical study of neuronal markers in human gingiva with phenytoin-induced overgrowth.

The immunohistochemical occurrence of several different neuronal markers has been investigated in human gingiva with phenytoin-induced overgrowth. The material was compared to gingival material taken following surgical orthodontic treatment. Gingiva obtained from the phenytoin-treated groups seemed to have a reduced number of neurofilament (NF) immunoreactive nerve fibers in the propria compared to control material. In both phenytoin as well as control gingiva sparsely distributed, thin, calcitonin gene-related peptide (CGRP) and substance P (SP) immunoreactive fibers were found in the propria. No obvious differences between the two groups could be observed for CGRP and SP. Immunoreactive cells for somatostatin (SOM) with a dendritic cell shape were found in the propria in both groups, sometimes in densely packed clusters. A tendency for increase of SOM-immunoreactive cells in the phenytoin-treated gingiva was observed. A few gamma-melanocyte stimulating hormone (gamma-MSH)-immunoreactive cells with a round appearance were found in control as well as phenytoin-affected gingiva. In one instance, however, a heavy gamma-MSH-immunoreactive cell infiltration was seen in the phenytoin sample. No immunoreactivity in either the phenytoin-treated group or in the control group was seen for proctolin or galanin. The results indicated that gingiva with phenytoin-induced overgrowth has a reduced innervation density revealed with NF immunohistochemistry.

Adolescent↗

Influence of renal denervation on vascular responsiveness of isolated rat intrarenal arteries.

Microsurgical renal denervation of the rat has been reported to increase blood loss and bleeding time after a standardized kidney resection. To investigate the vascular effects of denervation, isolated intrarenal arteries were studied using sensitive 'isometric' recording equipment. Four pieces of evidence were obtained to indicate an effective functional denervation I week after renal nerve transection: (i) Phentolamine reduced the K+-induced contraction in controls but not in denervated arteries. (ii) The K+-induced contraction was significantly smaller in denervated than in control arteries. (iii) Noradrenaline (NA) was a significantly more potent vasoconstrictor (4 x) in denervated than in control arteries. (iv) Cocaine increased the NA sensitivity in control arteries (3 x), whereas it failed to do so in denervated vessels. Vasopressin, 5-hydroxytryptamine (5-HT), NA (in the presence of cocaine), prostaglandin F2 alpha (PGF2 alpha) and dopamine (DA) produced concentration-dependent contractions in the mentioned order of potency. Denervated arteries were found to be about two to three times more sensitive to the vasoconstrictors than control arteries. Angiotensin I and II had no contractile effect in any of the vessel segments examined. Indomethacin-pretreated arteries also failed to respond to angiotensin II. Neuropeptide Y produced only weak contractions and failed to influence the NA concentration-response relationship in either control or denervated arteries. In conclusion, renal denervation caused a general supersensitivity of the vascular smooth muscle cells to both circulating and non-circulating vasoconstrictors. Our results cannot explain the increased blood loss and bleeding time seen after denervation, but rather support the view that the enhanced bleeding was caused by an interrupted vasoconstrictor influence of the sympathetic nerves.

Angiotensins↗

Light and electron microscopic immunocytochemical demonstration of intraepidermal CGRP-containing nerves in human skin.

The distribution of nerves immunoreactive to calcitonin gene-related peptide (CGRP) was studied in human skin with special reference to the intraepidermal nerve fibres. It was shown by light and electron microscopy that a small proportion of the CGRP immunoreactive nerves entered the epidermis. The majority of the nerves ended as free nerve terminals subepidermally. Intraepidermal nerve endings were mainly seen in skin areas, which have a dense sensory innervation, such as fingertips and foreskin. The role of the peptidergic nerves in human skin is discussed.

Calcitonin Gene-Related Peptide↗

Immunohistochemical evidence for the presence of somatostatin-containing sensory nerve fibres in the human skin.

Somatostatin-like immunoreactivity has been found to occur in nerve terminals and fibres of the normal human skin using immunohistochemistry. The immunoreactivity seemed predominantly to be associated with sensory nerves. Thus, nerve fibres displaying weak or moderately strong somatostatin immunofluorescence were observed as free nerve endings of the epidermis and as nerve fibres in the dermis. The immunoreactive nerves were found in low numbers in skin from arm, back and chest, however, only single fibres were seen in sensory specialized areas, such as fingertips. Very few fibres were found close to e.g. blood vessels and sweat glands. Somatostatin, generally believed to be a strongly inhibitory substance, should also be considered when examining the role of different sensory chemical messenger candidates in the human skin.

Histocytochemistry↗

T lymphocyte subpopulations in bone-marrow-transplanted patients in relation to graft-versus-host disease and cytomegalovirus-induced infection.

T cell subpopulations were studied in peripheral blood from 62 bone marrow recipients using monoclonal antibodies and flow cytometry. Patients with acute graft-versus-host disease (GVHD), patients with chronic GVHD, and patients with cytomegalovirus (CMV) infection had decreased OKT4/8 ratios. The data suggest that in GVHD this was due to reduced absolute numbers of OKT4-positive cells. CMV-infected patients had significantly increased numbers of OKT8-positive cells. Monitoring of T cell subpopulations was not informative for diagnosis or prognosis of acute GVHD in the single patient. CMV infection should be suspected at a sudden increase in the number of OKT8-positive cells.

Blood Preservation↗

Phenylethanolamine N-methyltransferase-like immunoreactivity in psoriasis. An immunohistochemical study on catecholamine synthesizing enzymes and neuropeptides of the skin.

Immunoreactivity for phenylethanolamine N-methyltransferase (PNMT), the enzyme involved in the conversion of norepinephrine to epinephrine, was present in the basal epidermis and upper dermis in 16 patients with psoriasis. The amount of immunoreactivity was increased tenfold in involved compared to uninvolved skin as characterized by computer-assisted image analysis. In skin from healthy volunteers no immunoreactivity could be found. In our subjects, no immunoreactivity was observed for the other catecholamine synthesizing enzymes (tyrosine hydroxylase; dopa-decarboxylase; dopamine-beta-hydroxylase), apart from single tyrosine hydroxylase positive adrenergic vascular nerves. Furthermore, in psoriasis, the immunoreactivity pattern of the peptides somatostatin, substance P, vasoactive intestinal polypeptide and bombesin was in agreement with skin from healthy volunteers.

Adult↗

Stimulative effect of somatostatin on cell proliferation in cultured chondrocytes.

We have earlier demonstrated that human growth hormone stimulates DNA synthesis and proteoglycan production in cultured chondrocytes. The present study is concerned with the effects of somatostatin and other neuropeptides on cell proliferation by cultured rat rib growth plate chondrocytes. Chondrocytes were isolated from the growth plates by collagenase digestion and cultured as monolayers in multiwell plates. The cells were allowed to attach overnight and subsequently incubated for 24 h under serum-free conditions to establish growth arrest. Somatostatin and other peptides were then added and the cultures were incubated for 18 h. Finally, the cultures were labelled for 6 h with tritiated thymidine in the presence of peptide. For screening purposes, the effect on DNA-synthesis was assayed as incorporation of [3H]-thymidine into acid-insoluble material. For a more exact estimate, parallel cultures were prepared for autoradiography and the fraction of labelled nuclei was determined by counting. Among the peptides we tested (somatostatin, GRF, TRH, SP, mENK, PHI, VIP, hCT) only somatostatin had any discernible effect on DNA synthesis, with an apparently optimal effect at 10 fM. This concentration is well within the range found in various tissues in vivo and suggests a physiological role for somatostatin in chondrocyte growth regulation. Further experiments are required, however, to clarify by which mechanism somatostatin influences the cells and whether the peptide interacts with other growth factors such as the IGFs.

Animals↗