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Biomedical subjects

Y Konttinen

Publications and source records attributed to Y Konttinen.

At least 19 recordsLinked to original sources
PubMed2001

Use of muscarinic agonists in the treatment of Sjögren's syndrome.

Two muscarinic agonists (pilocarpine and cevimeline) have recently been approved for the treatment of symptoms of xerostomia in Sjögren's syndrome (SS). These agents stimulate the M1 and M3 receptors present on salivary glands, leading to increased secretory function. The use of these agents emphasizes the importance of neuroendocrine mechanisms in SS, which is considered an autoimmune disorder. We review recent studies on the release of cytokines and metalloproteinases in SS-affected glands and their influence on the release of and response to neurotransmitters. Also, we review the structure and function of muscarinic receptors as they may relate to SS and the potential use of novel muscarinic agonists in SS.

Humans↗
PubMed2000

Integrity and full coding sequence of B19 virus DNA persisting in human synovial tissue.

Primary infection by human parvovirus B19 is often accompanied by arthropathy of varying duration, of which the most severe cases can be indistinguishable from rheumatoid arthritis (RA). While this might seem to imply a role in RA pathogenesis, recent studies have verified long-term persistence of B19 DNA in synovial tissue not only in patients with rheumatoid or juvenile arthritis, but also in immunocompetent, non-arthritic individuals with a history of prior B19 infection. However, the latter data are based on PCR amplification of short segments of DNA, with little sequence information. We determined the nucleotide sequence and examined the integrity of the protein-coding regions of B19 genomes persisting in synovial tissue and compared the results with data from synovial tissues of recently infected patients. In synovium of both previously and recently infected subjects, the viral coding regions were found to be present in an apparently continuous, intact DNA molecule. Comparison with sequences reported from blood or bone marrow showed that the synoviotropism or persistence of the B19 virus DNA was not due to exceptional mutations or particular genotype variants. The synovial retention of full-length viral genomes may represent a physiological process functioning in long-term storage of foreign macromolecules in this tissue.

Base Sequence↗
PubMed2000

[Musculoskeletal tissue engineering with resorbable polymers].

Musculoskeletal tissues can present congenital or acquired defects as a result of disease, accidental trauma or iatrogenous causes. This loss of bony substance is traditionally treated by the replacement of bony tissue (grafts or flaps), or by synthetic materials. Each of these methods of treatment, however, entails its specific disadvantages, limitations and complications. The recent approach for treatment of musculoskeletal defects has been the development of the growing of neotissues derived from autogenous cells, and artificial biodegradable matrixes. This method assumed the name "tissue engineering" in the late 1980s. Tissue Engineering, or TE, has employed advances made in the area of cellular culture, intercellular matrix biology, and also, in the area of biomaterial science. TE is an multi-disciplinary approach. Musculoskeletal TE, although in its preliminary stages, should allow access to treatments of the future.

Biocompatible Materials↗
PubMed1999

Mutational analysis of the HGO gene in Finnish alkaptonuria patients.

Alkaptonuria (AKU), the prototypic inborn error of metabolism, has recently been shown to be caused by loss of function mutations in the homogentisate-1,2-dioxygenase gene (HGO). So far 17 mutations have been characterised in AKU patients of different ethnic origin. We describe three novel mutations (R58fs, R330S, and H371R) and one common AKU mutation (M368V), detected by mutational and polymorphism analysis of the HGO gene in five Finnish AKU pedigrees. The three novel AKU mutations are most likely specific for the Finnish population and have originated recently.

Alkaptonuria↗
PubMed1998

Neuropeptides and steroid hormones in arthritis.

Primary afferent nociceptive and peptidergic efferent nerves are sensitized in arthritis and thus easily stimulated by mechanical and chemical stimuli. This leads to increased or disturbed release of neuropeptides from nerve terminals. This local (at the site of stimulation), expanded (expanded and additional receptive fields), and remote (cross-spinal reflexes) neuropeptide release leads to disturbed tissue homeostasis and neurogenic inflammation. In arthritis, raised levels of neuropeptides were detected in the synovial fluid, whereas nerve fibers were lacking in the synovial tissue. It has been hypothesized that cycles of nerve fiber destruction and degeneration follow the cycles of joint inflammation. This evidence suggests that the peripheral nervous system, through its neuropeptides, may contribute to the generation of inflammation, i.e., "neurogenic inflammation." Altered hypothalamic-pituitary-adrenocortical axis function and sex hormone status have been suggested to contribute to the development and persistence of arthritis. In particular, current evidence indicates that glucocorticoid secretion is closely and reciprocally interrelated with inflammation, and that an adrenal insufficiency is present in many forms of immune-mediated arthritis. Conversely, gonadal steroids seem to play a central role as predisposing factors in many forms of arthritis, with estrogens involved as immuno-enhancing hormones and androgens as natural immunosuppressors. Functional receptors for sex hormones have been described in cells involved in the immune response and, after activation, the hormone-receptor complex might modulate the expression of selected cytokines. The possibility of targeting the efferent nerves with specific peptides and replacement therapies with selected steroid hormones may represent a new and potentially efficient and natural system of modulation of the arthritis.

Animals↗
PubMed1998

Polymorphonuclear elastase in human colorectal carcinoma.

proteinases are required for invasion through the extracellular matrix (ECM) during tumor invasion and metastasis. Polymorphonuclear (PMN) elastase can degrade ECM components and modulate other proteinases. In the present study PMN elastase activity was found in tissue extracts from 8 of 15 human colorectal carcinomas. Immunoreactive PMN elastase was demonstrated in all carcinoma biopsies with particular enrichment at the tumor-host interface. Immunofluorescence staining localized immunoreactive PMN elastase mainly to neutrophile granulocytes. The human colon carcinoma cell lines Caco-2 and HT-29 did not express PMN elastase. An interaction between tumor cells and elastase producing leukocytes is suggested.

Adenocarcinoma↗
PubMed1998

Macrophage activation results in bone resorption.

Monocytes or macrophages from important accessory cells in the regulation of bone metabolism and destruction. Cells of the mononuclear phagocyte lineage form the precursor cells of the osteoclasts. Soluble products produced by activated macrophages regulate progenitor cell proliferation, recruitment, differentiation, and activity of osteoblasts and osteoclasts. After osteoclasts are removed from the resorption site, macrophages process bone surfaces and create a cement line before osteoblasts enter to form new bone. Although osteolysis associated with normal bone remodeling is seen as an osteoclast driven process, it may be that in chronic inflammation macrophage activation and vascular derangements lead to low pH, local bone demineralization (acid attack), and H+ mediated stimulation of the primary afferent nociceptive nerve fibers (bone pain). Osteoclasts are not able to attach to demineralized bone or to osteoid surfaces. However, if macrophages degrade the demineralized organic bone matrix, chemotactic factors and attachment sites for osteoclasts are produced. In such a scenario, the osteoclast-osteoblast mediated activation, resorption, and formation cycle would be secondarily activated. Such events may play a role in the most common orthopaedic problem related to macrophage activation, aseptic loosening of orthopaedic joint implants, which is secondary to a chronic foreign body reaction and to micromovement.

Bone Resorption↗
PubMed1996

Neuropeptides and the puzzle of bone remodeling. State of the art.

Bone metabolism is dependent on cells of the osteoblast and osteoclast lineage. These cells play a major role in the synthesis and degradation of osteoid and in its mineralization and demineralization. Bone cells are under the influence of various systemic and local auto/paracrine factors. One further regulatory element that can play both a sensory/ afferent and a regulatory/efferent role, consists of neuropeptide-containing nerves. In particular, the calcitonin gene-related peptide (CGRP) and vasoactive intestinal peptide (VIP) have been implicated; their distribution in bone and their molecular biology are discussed in some detail. Bone neuropeptides can function as direct bone cell regulators, with additional amplifying indirect effects mediated by vascular endothelial cells, monocyte/macrophages and mast cells and their mediators. Recent experimental and clinical work has implicated bone nerves in processes varying from normal remodelling to fracture healing and non-union. Apart from systemic endocrine influences on bone stock and osteoclast/ osteoblast coupling (activation-resorption-formation cycle) mediated by local auto/paracrine factors, bone nerves/neuropeptides may explain why various inputs/outputs are transformed in a meaningful way to altered mass and quality of bone.

Bone Remodeling↗
PubMed1994

Influence of various experimental parameters on the incidence of thermal and mechanical hyperalgesia induced by a constriction mononeuropathy of the sciatic nerve in lightly anesthetized rats.

In the current investigation we examined a peripheral mononeuropathy induced by four loose ligatures around the sciatic nerve. The nerve was treated with lidocaine or saline before implementing the ligatures (silk or chromic gut). The latency of the hindlimb withdrawal to noxious mechanical and radiant heat stimuli was tested under light pentobarbital anesthesia 3-10 days following the surgery. A latency/threshold difference > or = 15% between the hindlimbs was considered to represent a change in the nocifensive response. The adapting skin temperature of the hindlimbs was also measured. Pieces of hindpaw skin and the sciatic nerve were taken for histological evaluation. The results indicate that the incidence of hyperalgesia induced by a constriction mononeuropathy depended on the noxious submodality tested, and that the thermal and mechanical hyperalgesia were not coupled in all cases. Use of only one test modality led to false negative results. Furthermore, mononeuropathy-induced changes in the adapting skin temperature produced a considerable number of false positive results (an artefactual hyperalgesia) when radiant heat alone was used to determine the nocifensive withdrawal latency without paying attention to the abnormality of the skin temperature. A preemptive lidocaine treatment of the sciatic nerve before the nerve ligation significantly reduced the incidence of mononeuropathy-induced hyperalgesia. The nerve ligation material (silk vs chromic gut) was not a significant factor for the development of hyperalgesia induced by a constriction injury of a peripheral nerve. In histological evaluation the constriction injury-induced damage of the sciatic nerve was verified, and the inflammatory reaction caused by chromic gut was not stronger than that caused by silk ligatures. In general, immunohistochemical staining for substance P decreased whereas that for VIP increased. The results support the hypothesis that ligation-induced mechanical trauma and the afferent barrage induced by it, especially during the perioperative period, plays an important role in the development of postoperative hyperalgesia.

Adaptation, Physiological↗
PubMed1993

Effect of zopiclone on sleep quality, morning stiffness, widespread tenderness and pain and general discomfort in primary fibromyalgia patients. A double-blind randomized trial.

Thirty-three patients fulfilling the diagnostic criteria for primary fibromyalgia completed an eight-week double-blind treatment trial with the drug zopiclone. Of outcome measures studied a score expressing subjective sleep quality showed improvement in more than ninety percent of zopiclone patients at 4 weeks and nearly eighty percent at 8 weeks, but similar improvement was also reported by more than sixty percent of the patients on placebo. Patient self-assessment of a treatment effect also showed an advantage for zopiclone, with most patients in the placebo group considering their state as unchanged at 8 weeks. According to examiner assessment, however, half the patients in both groups showed improvement at 8 weeks. For other assessment variables, e.g. dolorimeter assessment of widespread tenderness, visual analogue scales and pain drawings for pain and other subjective feelings of discomfort, the effects of zopiclone treatment were at the same level as those of placebo.

Adolescent↗
PubMed1990

MS and SLE in twins of successive generations.

During a nationwide twin study on multiple sclerosis (MS) in Finland a dizygotic pair discordant for MS was found. The affected co-twin had dizygotic twin daughters. The affected co-twin of the second generation had systemic lupus erythematosus (SLE). Both pairs were thoroughly examined. No evidence of CNS involvement in the healthy co-twins was found. In pairwise comparisons, virus-specific IgG antibodies to measles and mumps were significantly increased in the MS patient whereas the same was true for rubella in the SLE patient. Both MS and SLE patient expressed HLA alleles most often found to be associated with these disorders. Reversed CD4/CD8 ratios were observed in both MS and SLE patient. No difference in interleukin-2 receptor expression were found but gamma-interferon secretion in the MS patient showed marked increase whereas that of the SLE patient was of the same magnitude as in the healthy members. A different triggering stimulus rather than the dissimilarity in the immunogenetic predisposition may be decisive as to whether or not they develop MS or SLE.

Adult↗
PubMed1990

Hip arthroplasty infection. Current concepts.

Due to systemic or local antibiotic treatment and other preventive procedures, the incidence of deep hip-prosthetic infections in Scandinavia is less than 1 percent, with the majority hematogenous. Coagulase-negative staphylococci and anaerobes are involved in more than half of the cases. The diagnosis is sometimes difficult; preoperative aspiration often gives misleading results; and granulocyte scanning usually adds valuable information. In deep infection the current strategy is to revise with a two-stage procedure. Revisions should be carried out at specialized centers with bacteriologic competence and sufficient experience with implants.

Bacterial Infections↗
PubMed1990

[Strategy in endoprosthesis infections].

Infection in total hip replacement, its definition, normal history and treatment are reviewed. A case with a two stage revision with the use of a cementless resection prosthesis is presented.

Femur↗
PubMed1987

Ultrastructure of oral leukoplakia and lichen planus. II. A correlated scanning and transmission electron microscopic study of epithelial surface cells.

Nine cases of homogenous leukoplakia and 21 cases of lichen planus (11 reticular and 10 erosive) were studied under the scanning and transmission electron microscopes. Characteristic differences between leukoplakia and lichen planus in surface patterns of the epithelial surface cells were noted. Microridges in leukoplakia form parallel and anastomosing rows whereas the picture in lichen planus is irregular with microridges varying in width. The transmission electron microscopic findings confirm and correlate with these findings, the microridges representing invaginations of the plasma membrane. The keratin patterns exhibited by the surface cells were also characteristic regarding type and site of lesion. Scanning electron microscopy can be used as an additional diagnostic aid in differentiating these lesions.

Epithelium↗
PubMed1987

Ultrastructure of oral leukoplakia and lichen planus. I. Basal region and inflammatory cells.

Nine cases of homogenous leukoplakia and 21 cases of lichen planus (11 reticular and 10 erosive) were studied under the electron microscope. The changes found in leukoplakia were limited to occasional breaks in the basal lamina and modest changes in the cytoplasm of the basal cells. The basal lamina in lichen planus was found to exhibit 3 distinctly different pictures reflecting the clinical types of lichen planus. The structural abnormalities in the basal cells increased with increasing severity of the lesions. The inflammatory infiltrate in lichen planus was found to contain mainly small-to-medium-sized lymphocytes but plasma-cells with widely dilated rough endoplasmic reticulum containing a granular substance were frequently seen. Similar changes are seen in other disorders and, therefore, specific diagnostic criteria cannot be established on the basis of the present material.

Basement Membrane↗