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Biomedical subjects

K Holmberg

Publications and source records attributed to K Holmberg.

At least 73 records · Page 4Linked to original sources

Case report and review of disseminated histoplasmosis in South-East Asia: clinical and epidemiological implications.

The South-East Asian region is not known to be a major endemic area for histoplasmosis. We have recently diagnosed several cases of disseminated histoplasmosis in patients from this region. We report on a well documented indigenous case of disseminated histoplasmosis in a 62-year-old poultry farmer and review the literature for other reported cases of clinical histoplasmosis in the South-East Asian region. Sporadic cases of indigenous chronic pulmonary and non-meningeal disseminated histoplasmosis in immunocompetent hosts have been reported as well as examples of disseminated histoplasmosis in immunocompromised hosts. These reports suggest that histoplasmosis is endemic to certain areas in South-East Asia and that there may be a large number of undiagnosed and subclinical cases. The recent advances in diagnostic tests for histoplasmosis are also reviewed with reference to the experience of using these tests in the reported case.

Amphotericin B↗

Nasal polyps: medical or surgical management?

Nasal polyposis is considered to be a non-IgE-mediated inflammatory condition of the nose and sinuses, often associated with chronic non-allergic rhinitis, aspirin intolerance and non-allergic asthma. The aetiology of nasal polyposis is unknown. The main symptoms are nasal obstruction and disturbance of the sense of smell. Occlusion of the nasal passage by a few large polyps could be treated by simple polypectomy to help the patient breathe through the nose. Polypectomy per se does not worsen asthma. Other surgical procedures can be performed, depending on the degree of the disease. The aim of surgery is to restore the physiological properties of the nose by making the nose as free from polyps as possible, and to allow drainage of infected sinuses. Complementary medical treatment of polyposis is always necessary, as surgery cannot treat the inflammatory component of the mucosal disease. In this respect, topical corticosteroids have long been the drugs of choice to reduce the size of polyps, to prevent recurrence after surgery, and are often the main treatment for the disease in many patients. Fluticasone propionate has now been shown to be at least as effective as beclomethasone dipropionate as a medical tool in the management of polyposis. Short-term treatment with systemic corticosteroids is an alternative method of inducing remission and controlling nasal polyps. However, in most patients with nasal polyps, treatment consists of both medical and surgical management.

Humans↗

Localization of choline acetyltransferase in rat peripheral sympathetic neurons and its coexistence with nitric oxide synthase and neuropeptides.

Indirect immunofluorescence methods using a mouse monoclonal antibody raised to rat choline acetyltransferase (ChAT) revealed dense networks of ChAT-immunoreactive fibers in the superior cervical ganglion, the stellate ganglion, and the celiac superior mesenteric ganglion of the rat. Numerous and single ChAT-immunoreactive cell bodies were observed in the stellate and superior cervical ganglia, respectively. The majority of ChAT-immunoreactive fibers in the stellate and superior cervical ganglia were nitric oxide synthase (NOS) positive. Some ChAT-immunoreactive fibers contained enkephalin-like immunoreactivity. Virtually all ChAT-positive cell bodies in the stellate ganglion were vasoactive intestinal polypeptide (VIP)-positive, and some were calcitonin gene-related peptide (CGRP)-positive. After transection of the cervical sympathetic trunk almost all ChAT- and NOS-positive fibers and most enkephalin- and CGRP-positive fibers disappeared in the superior cervical ganglion. The results suggest that most preganglionic fibers are cholinergic and that the majority of these in addition can release nitric oxide, some enkephalin, and a few CGRP. Acetylcholine, VIP, and CGRP are coexisting messenger molecules in some postganglionic sympathetic neurons.

Animals↗

Protein-rejecting ability of surface-bound dextran in end-on and side-on configurations: comparison to PEG.

There is much interest in attaching polyethylene glycol (PEG) and other hydrophilic, neutral polymers to surfaces to reduce the extent of protein and cell adsorption. Interestingly, these same surface-bound polymers are effective in masking surface charge and reducing electrokinetic effects such as particle electrophoretic mobility, streaming potential, and electroosmosis. It is apparent that similar molecular properties are responsible for both protein and cell rejection and reduction of electrokinetic effects. In this work we compared the fibrinogen-rejecting ability and the effect on electrophoretic mobility of three polymer coatings bound to polystyrene. The three polymers were side-bound dextran, end-bound dextran, and end-bound PEG. The results of these measurements were used to elucidate the importance of polymer packing density and polymer layer thickness on protein adsorption and reduction of electrokinetic effects. Protein adsorption appears not to be sensitive to polymer layer thickness or the presence of dilute polymer tails in a surface coating, while electrokinetic effects are. Protein adsorption is, however, very sensitive to the availability of exposed surface. Finally, the unique effectiveness of PEG is apparent in this research as in previous studies.

Adsorption↗

Comparative study of the GenePath group 4 reagent system and other CHEF systems for karyotype analysis of Candida spp.

The commercial GenePath Group 4 Reagent Candida kit (BioRad), designed to simplify the electrophoretic karyotyping of Candida spp. was evaluated against several other established contour-clamped homogeneous electric field (CHEF) systems for Candida. This comparison allowed assessment of both the GenePath system and the other CHEF systems regarding the sources of technical variability of the assays and variation in karyotypic analysis. The GenePath system appeared to be a simple, rapid and reliable tool for karyotyping of Candida spp. with a discriminatory power comparable with established CHEF systems. The evaluation showed that the variability of the CHEF systems for subtyping of Candida is largely a function of technical variabilities in the assay system (reagents, sample preparation, running conditions, and test performance), and of analytical variabilities due to imprecision or observers bias. Lack of standardization of these factors may contribute to variability among investigators and have an impact on the ultimate conclusions of an epidemiological study using CHEF methods.

Candida↗

Delayed chromosomal instability in human T-lymphocyte clones exposed to ionizing radiation.

Recent studies have demonstrated that cells which survive alpha-particle and X-ray exposure may show chromosomal instability, i.e. they continue to develop chromosomal aberrations at an increased frequency for many division cycles after the exposure. To characterize this delayed response, we carried out repeated karyotype analyses of X-irradiated T-lymphocytes during clonal expansion in vitro. Human peripheral blood lymphocytes were obtained from a healthy donor and exposed to 3-Gy X-irradiation. Cell survival, estimated by a cell cloning assay, was 5%. Non-irradiated, control cells were studied in parallel. Monoclonal cell lines were established using the T-cell cloning procedure. G-band karyotype analyses were carried out at several intervals during expansion of the clones for up to 2 months. The irradiated clones did not differ from the control clones with regard to growth rate or cytometric DNA profile. Non-irradiated cell clones showed a normal karyotype, with < 10% of sporadic, non-clonal chromosome and chromatid breaks. In the irradiated clones, the karyotypes showed different (sub)clonal chromosome rearrangements, which developed successively during the cultivation time. In addition to these karyotypic abnormalities, > 20% of the cells in these clones had sporadic, non-clonal chromosome aberrations, and there was a tendency of increasing frequency of such aberrations by length of cultivation. Thus, two types of radiation-induced chromosomal instability were observed; (sub)clonal karyotypic abnormalities and sporadic, non-clonal chromosome aberrations. The frequency and kinetics by which these alterations occur in the progeny of X-irradiated T-cells suggest that they arise through different pathways, and argue against their causation by mutation or persistent DNA damage.

Cell Division↗

Annoyance and discomfort during exposure to high-frequency noise from an ultrasonic washer.

Annoyance and discomfort during exposure to high-frequency noise from an ultrasonic washer have been examined in the experiments carried out with 10 subjects. After a short exposure during which the subjects rated their annoyance and discomfort, a broad-band noise was matched to the ultrasound. The subjects were exposed to three different levels of ultrasound on three different occasions. Analyses showed that ultrasound causes considerable annoyance and discomfort even for the lowest exposure levels. No significant difference between annoyance and discomfort was observed. The matchings indicated, however, that the A-weighting, i.e., the traditional rating technique used for noise evaluations, overestimated the high-frequency sound when evaluating annoyance and discomfort.

Adult↗

Ubiquinone-10 protects neurons from virus-induced degeneration.

Cultured neurons from rat dorsal root ganglia and cerebral cortex were infected with Sendai virus, which gives a productive replication with lysis of most neurons, and with the RW strain of mumps virus, which undergoes defective replication causing degeneration of only 30-40% of the neurons within 5 days after initial infection. In Sendai virus-infected cells the amount of polyisoprenoid lipids was enhanced. In mumps virus-infected cultures there were transient reductions in the contents of cholesterol, dolichol, and ubiquinone-9 in the cultures, whereas the reduction in the ubiquinone-10 level was progressive, reaching 20% of its original value 21 days after infection. Treatment of mumps virus-infected cultures with ubiquinone-10 protected the neurons from degeneration, whereas no effects were observed on exposure to ubiquinone-9. Linolenic acid (18:3) and arachidonic acid (20:4), but not myristic acid (14:0) and palmitic acid (16:0), also had significant neuroprotective effects.

Animals↗

Effects of branching and molecular weight of surface-bound poly(ethylene oxide) on protein rejection.

To understand better the origin of protein rejection observed with surface-bound poly(ethylene oxide) (or PEO), we have measured fibrinogen adsorption for a series of linear and branched, low-molecular-weight PEOs bound to solid polystyrene surfaces. The results show that a dependence on molecular weight is found below 1500 g mol-1 for linear PEO. Branched PEOs are less effective at protein rejection than linear PEOs. The branched PEOs have smaller exclusion volumes (from GPC) than the corresponding linear PEOs, consistent with restriction in conformational freedom for the branched compounds. The protein rejection results are interpreted in terms of entropy changes that result upon protein adsorption. In addition, some practical problems in preparation of PEO glycidyl ethers have been clarified, thus making these PEO derivatives more useful for surface modification.

Adsorption↗

Does allergic rhinitis predispose to sinusitis?

The relationship between allergic rhinitis and sinusitis is reviewed with regard to seasonal as well as perennial and fungal sinusitis. There seems to be some association between allergic processes in the nose and inflammation in the sinus mucosa but the available data are, to some extent, contradictory. Thus, the causative role of allergy in sinusitis is not clear. Prospective studies to further elucidate the influence of allergic inflammation in the pathogenesis of sinusitis are highly warranted.

Causality↗

Influence of degradable starch microspheres on the human nasal mucosa.

The effect of the nasal administration of degradable starch microspheres (DSM) on the mucociliary system and the geometry of the nasal cavities were evaluated in 15 healthy volunteers. The baseline values for mucociliary clearance of the right nasal cavity were determined on two separate days for each subject using the saccharin-dyes test. Acoustic rhinometry was performed before and during the saccharin-dyes test. The patients then started the treatment period and inhaled 10 mg of DSM intranasally once daily in each nostril for 8 days. The saccharin-dyes test was performed 5 min after the deposition of the DSM on day 1 and day 8. The geometry of the nasal cavities was determined before, 7 min after deposition, and after the end of the saccharin test. Both tests were also performed two days after the end of the treatment period. Each subject was examined by means of rhinoscopy on every visit during the investigation. No changes in mucociliary clearance or in the geometry of the nasal cavities were found after repeated administration of starch microspheres. Thus, intranasally-administered degradable starch microspheres did not have an adverse effect on human nasal mucociliary clearance, and the DSM did not cause any congestion or decongestion of the mucosa.

Administration, Intranasal↗

Microtubule-associated protein 2 appears in axons of cultured dorsal root ganglia and spinal cord neurons after rotavirus infection.

The immunohistochemical distribution of microtubule-associated protein 2 (MAP2), being normally restricted to nerve cell bodies and dendrites, became altered in rat dorsal root ganglia and spinal cord neurons in cultures infected with rhesus rotavirus. MAP2 appeared in axons of both sources of neurons as displayed with monoclonal antibodies to MAP2a + b and MAP2a + b + c at 48 hr post-infection (p.i.). Other cytoskeletal elements, i.e., tau, MAP1, MAP5, neurofilament, actin, and tubulin, did not reveal any alterations in the rotavirus-infected neurons. One of the rotavirus cytosolic proteins, the inner capsid protein vp6, was expressed in axons at 48 hr p.i. simultaneously with the appearance of MAP2, while two other viral proteins, vp4 and NS28, remained in the nerve cell bodies. By quantitative enzyme-linked immunosorbent assay (ELISA) a binding of single-shelled rotaviruses, which express vp6 on their surfaces, to purified MAP2 was found. There was no binding of these viral particles to tau or tubulin proteins. This study indicates that a selective interaction between certain viral and neuronal cytoskeletal proteins can occur and that a non-cytolytic viral infection can cause alterations in the polarized sorting of neuronal proteins.

Animals↗

Clonal chromosome aberrations and genomic instability in X-irradiated human T-lymphocyte cultures.

To study the effects of X-irradiation on clone forming ability and karyotypic abnormalities in human peripheral blood lymphocytes, cells were exposed to 3 Gy of X-rays in vitro and either individual T-cell clones or long-term T-cell cultures were established. The karyotypes were analyzed in G-banded chromosome preparations after proliferation for 9-34 days in vitro. T-cell clonal karyotype abnormalities were found in 24 of 37 (65%) irradiated and in two of 43 (5%) control clones. Balanced reciprocal translocations and deletions were the predominating types of clonal aberrations. Complex aberrations and unstable karyotypes were found in about half of the irradiated clones. Some of the T-cell clones demonstrated sequential change from normal to aberrant karyotype. Other clones seemed to develop multiple, heterogeneous chromosomal aberrations during growth in vitro. X-Irradiated T-cells grown in long-term T-cell culture displayed karyotype abnormalities in 60-80% of the cells, and the types of aberrations were similar to those found in the individual, irradiated T-cell clones. An increasing number of cells with the same abnormal karyotype was observed when the cultivation time was extended, indicating clonal proliferation. These results demonstrate that a surprisingly high proportion of T-cells with stable and often complex irradiation-induced chromosome aberrations are able to proliferate and form expanding cell clones in vitro. Furthermore, the results indicate that X-irradiation induces latent chromosome damage and genomic instability in human T-lymphocytes.

Adult↗

Mast cells and mediators in the nasal mucosa after allergen challenge. Effects of four weeks' treatment with topical glucocorticoid.

The study focuses on the relationship between the tissue density of mast cells, the tissue histamine levels and the levels of markers of mast cell activation after an allergen challenge of the nasal mucosa of allergic patients. The effect of 4 weeks' treatment with a topical glucocorticoid, fluticasone propionate, was studied in a double-blind, placebo-controlled study of 25 hay fever patients. Nasal biopsies were obtained before and after the treatment period for the evaluation of mast cell density and tissue histamine levels. Nasal challenges were performed at 2-week intervals for 8 weeks using a standardized nasal lavage model. TAME-esterase was analysed in the returned lavage fluid from all the challenges (weeks 0-8), while the levels of histamine and tryptase were analysed in lavage fluids from challenges performed before and after the treatment period (weeks 0 and 4). The symptoms of nasal allergy were assessed after each challenge. Treatment with fluticasone propionate did not influence mast cell density, the tissue histamine concentration, the lavage histamine levels or the TAME-esterase activity, while a reduction in nasal symptoms and tryptase in nasal lavage fluid was revealed. Our present study again emphasizes the fact that the mast cell is an important trigger cell in the immediate nasal allergic response. The study also demonstrates the usefulness of the measurements of tryptase as an indicator of both mast cell activation and the efficacy of topical steroid treatment.

Administration, Topical↗

A Trypanosoma brucei brucei-derived factor that triggers CD8+ lymphocytes to interferon-gamma secretion: purification, characterization and protective effects in vivo by treatment with a monoclonal antibody against the factor.

A protein factor that stimulates CD8+ lymphocytes to produce and secrete IFN-gamma has been purified from Trypanosoma brucei brucei (T.b. brucei). This was accomplished by raising monoclonal antibodies (MoAbs) against a fraction of T.b. brucei obtained by gel filtration, which contained high levels of material inducing rat mononuclear cells (MNC) to IFN-gamma production. MoAbs from four hybridomas strongly inhibited trypanosome-induced IFN-gamma production. One of them (MO1) was used for purification of the trypanosome-derived lymphocyte triggering factor (TLTF) by affinity chromatography. SDS electrophoresis of the purified TLTF displayed a band of 42-45 kDa MW. Gel filtration of homogenates of whole parasites yielded several peaks of IFN-gamma-inducing activity with a lowest MW of 41-46 kDa. Bioactivity of all peaks was blocked by MO1, suggesting that a single molecule, or a single epitope of additional molecules, is responsible for the different peaks with IFN-gamma-inducing activity. IFN-gamma released from MNC stimulates T.b. brucei growth. Blocking of TLTF in vitro with MO1 inhibited MNC-supported growth of the parasites. To study the in vivo relevance of TLTF in the course of experimental African trypanosomiasis, MO1 was used to treat rats and mice at different times after infection. Treatments instituted at different time-points after infection suppressed parasite growth, abrogated the IFN-gamma production by splenocytes induced by the infection and prolonged survival of the animals. The data support the hypothesis that TLTF and IFN-gamma have a crucial regulatory function in the parasite-host interactions and that these molecules influence the disease course during experimental African trypanosomiasis.

Animals↗