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Biomedical subjects

U Karlsson

Publications and source records attributed to U Karlsson.

At least 37 records · Page 2Linked to original sources
PubMed1997

Obese (ob) gene defects are rare in human obesity.

Our knowledge of the role of the recently cloned ob-protein (leptin) in the regulation of body fat stores is largely derived from experiments performed in mice. Different mouse models exhibit abnormalities in ob-gene expression, with extreme overexpression in mice which lack bioactive ob-protein, have nonfunctional ob-receptors or hypothalamic lesions, and undetectable expression in mice with suggested defects in regulatory elements. The aim of this study is to examine if defects, corresponding to those in mice, exist in human obesity. Adipose tissue was obtained from 94 adult obese subjects and from six children who had developed obesity after surgery in the hypothalamic region. Total RNA was isolated and ob-gene expression was examined by reverse transcriptase-polymerase chain reaction (RT-PCR) and Northern blot. The coding region of the ob-gene was sequenced in both directions in the 94 obese adults. No mutations were detected in the coding region of the ob-gene and ob-gene expression was detectable in all subjects and none of the subjects had an extreme overexpression. There was no systematic increase in ob-expression in obese children with hypothalamic disease compared to their healthy brothers and sisters. These results show that severe abnormalities involving the ob-gene, analogous to those described in mouse models, are rare in human obesity. We therefore conclude that the cloning and subsequent analysis of the ob-gene has not provided information that can, by itself, explain the genetic component in the development of human obesity.

Adipose Tissue↗
PubMed1996

Non-submerged implants in the treatment of the edentulous lower jar. A 2-year longitudinal study.

Non-submerged ITI Bonefit implants (ITI Dental Implant System) were inserted in edentulous lower jaws of 46 patients. The patients were provided with either a fixed prosthesis or an overdenture, and has been followed during a 2-year-period. At the 1-year examination, the suprastructures were removed permitting test of the individual implant stability. Radiographic examinations were performed in connection with the loading of the implants and at the 1-year examination. In total 216 implants were inserted. 4 implants were lost before loading and 4 during the 2nd year of function, which gives a survival rate after 1 year 98% and after 2 years of 96%. The mean marginal bone loss during the first year of function was 0.1 mm. However, the marginal bone changes had a high degree of variation and four implants showed a severe bone loss. The intention is to follow this patient group with annual examinations during 5 years.

Adult↗
PubMed1995

Ocular globe topography in radiotherapy.

PURPOSE: Ocular lens, retina, and olfactory bulb exposure are common concerns in contemporary radiotherapy practice. Methods to clinically localize soft tissue structures (i.e., lens and retina) are varied and often imprecise. We hypothesized that eyelid markers constituted a better reference point than the commonly used lateral canthus marker for lateral beam simulations, unless diagnostic computed tomography or ultrasound examinations were available and/or used. METHODS AND MATERIALS: Sixty-six pre-Magnetic Resonance Image, normal, orbital computed tomography scans from adult patients were used to measure (a) sagittal distances from eyelid to posterior lens surface, from lateral canthus to posterior lens surface and to the globe's posterior pole, (b) supero-inferior distances in the lateral projection from the lens to the cribriform plate, and (c) common dimensions to establish internal validity of the measurements. RESULTS: The eyelid to lens and retina topography is individually more constant than that from the canthus. There is little if any supero-inferior separation between the lens and the cribriform plate lateral projections. CONCLUSIONS: The lateral canthus does not specify lens or retina locations. Eyelid markers of known size provide more accurate anatomical information. Lateral beam ocular globe shielding has to be individualized. Lens shielding is questionable if the olfactory bulb needs to be irradiated by a lateral beam.

Adult↗
PubMed1995

Evaluation of implant-supported carbon/graphite fiber-reinforced poly (methyl methacrylate) prostheses. A longitudinal multicenter study.

Carbon/graphite fiber-reinforced poly (methyl methacrylate) (CGFP) has been suggested as an alternative framework material for implant-supported fixed prostheses. The aim of this study was to evaluate CGFP prostheses clinically over time in patients treated with titanium implants of the Brånemark type and to study the handling of the material in the technical production. Twenty-five patients were fitted with 27 CGFP prostheses supported by 119 implants. Three implants, all in the upper jaw, were lost after loading. After a mean functioning time of 44 months (range 32-56), 19 prostheses (70%) were still in situ. In all, 5 prostheses fractured, of which 3 were exchanged whereas 2 could be repaired. The fractures were discovered early after loading and located close to the end abutment cylinders. During the follow-up period, the bone loss around the implants was about the same as earlier reported values for fixed prostheses with cast frameworks. It is concluded that a CGFP framework can be used to form the biocompatible superstructure of implant-supported prostheses with high precision at a low material cost and with good aesthetic results. The mechanical properties are so far not satisfactory but the method has the potential to be further developed and standardized.

Adult↗
PubMed1994

(+/-)-CP-96,345, an NK1 receptor antagonist, has local anaesthetic-like effects in a mammalian sciatic nerve preparation.

The effect of the non-peptide NK1 receptor antagonist (+/-)-CP-96,345 was investigated on the compound action potential (cAP) recorded in the isolated guinea-pig nerve, and compared to the effects of the local anaesthetic lidocaine and the L-type Ca2+ channel antagonist diltiazem. (+/-)-CP-96,345, as well as lidocaine and diltiazem, produced a concentration dependent reduction of the cAP amplitude. All three drugs showed frequency dependent block. The block of the cAP by lidocaine was fully reversible at all concentrations tested, while the block by (+/-)-CP-96,345 and diltiazem were only partly reversible at higher concentrations. The present findings indicate that (+/-)-CP-96,345 exerts a local anaesthetic-like effect on nerve conduction.

Action Potentials↗
PubMed1994

Production of large amounts of recombinant interleukins by cDNA transfected mouse myeloma cells cultured in dialysis tubing.

Studies of interleukin function often require large quantities of these highly expensive substances. The available interleukins are generally recombinant proteins produced in bacteria or yeast and, less commonly, interleukins produced by mammalian cells, which provide appropriate glycosylation and other post-translational modifications. Due to differences in biosynthesis, difficulties in production and purification the quality of the interleukin preparations may vary. We have taken advantage of the recently developed constitutively interleukin-secreting mouse myeloma cell lines and the dialysis tubing culture technique, which permit cells to be grown at high densities, in order to establish a method for the production of large amounts of recombinant murine IL-2 and IL-4. We show that these interleukins can be produced at low cost and in concentrations 20-30-fold higher than in conventional culture flasks. A single dialysis tubing culture will produce more than 10(6) U of interleukin which may be compared with the available commercial preparations containing between 10- and a 100-fold less per vial. The IL-2 and IL-4 produced in this manner are biologically active molecules as demonstrated by the strong proliferative response of clonal T cells and the isotype-switching effect in LPS-stimulated splenic B cell cultures. The dialysis tubing culture technique is a simple and highly cost-effective means of generating large quantities of biologically active interleukins and is especially suitable for research laboratories interested in functional studies of these proteins.

Animals↗
PubMed1993

Systemic or intracerebroventricular injection of NMDA receptor antagonists attenuates the antinociceptive activity of intrathecally administered NMDA receptor antagonists.

We have previously reported that the response latency in the mouse hot-plate test is affected differently by spinal intrathecal (i.t.) injection of competitive and non-competitive N-methyl-D-aspartate (NMDA) receptor antagonists, in that only the former produces an antinociceptive effect. Since the lipophilic non-competitive antagonists will redistribute rapidly from the spinal injection site, it is conceivable that they reach sites where they counteract the spinal antinociceptive effect. In the present study, we have tested this hypothesis by comparing the antinociceptive effect of the competitive NMDA receptor antagonist CGS 19755 and the non-competitive NMDA receptor antagonist MK-801 after i.t., intraperitoneal (i.p.) and intracerebroventricular (i.c.v.) administration as well as after combinations thereof. CGS 19755 injected i.p. or i.c.v. and MK-801 injected i.p. or i.t. attenuated the antinociceptive effect of i.t. injected CGS 19755. Both i.p. and i.c.v. administration of either CGS 19755 or MK-801 dose-dependently impaired motor function without producing antinociceptive effects. Thus, the effect of CGS 19755 and MK-801 on the motor system was found to be separate from their antinociceptive effect. In a separate experiment, changes in hind-paw skin temperature were excluded as a possible confounding factor. These findings demonstrate that supraspinal systems can limit the spinal antinociceptive effect of NMDA receptor antagonists.

Animals↗
PubMed1992

Antinociceptive actions of different classes of excitatory amino acid receptor antagonists in mice.

Intrathecal (i.t.) injection of the competitive and selective N-methyl-D-aspartate (NMDA) receptor antagonists DL-2-amino-5-phosphonopentanoic acid (AP5), D-2-amino-7-phosphonoheptanoic acid (AP7), beta-D-aspartylaminomethyl phosphonic acid (Asp-AMP), 3-((+/-)-2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid (CPP) and gamma-D-glutamylaminomethyl phosphonic acid (Glu-AMP) produced dose-dependent and reversible analgesic effects in the mouse hot-plate and formalin tests of nociception. They were slightly more potent in the formalin test but had no or negligible effects in the tail-flick test. The non-selective or non-NMDA receptor antagonists 6-cyano-7-nitro-quinoxalinedione (CNQX), 6,7-dinitro-quinoxalinedione (DNQX), gamma-D-glutamylglycine (gamma DGG), gamma-glutamylaminomethyl sulphonic acid (GAMS), kynurenic acid, cis-2,3-piperidine dicarboxylic acid (cis-PDA; partial agonist) and p-bromobenzoyl piperazine dicarboxylic acid (pBB-PzDA) had the same efficacy in the mouse hot-plate, tail-flick and formalin tests (gamma DGG and pBB-PzDA were not tested in the formalin test). This heterogeneous group of antagonists was somewhat more potent in the tail-flick test and slightly less potent in the formalin test than in the hot-plate test. Of the two glycine site antagonists tested, 7-chlorokynurenic acid (7-Cl-Kyn) and (+/-)-3-amino-1-hydroxy-2-pyrrolidone (HA-966), the effect of the latter was compatible with selective action at the NMDA receptor complex while the action of the former was comparable to those of non-selective excitatory amino acid (EAA) receptor antagonists.(ABSTRACT TRUNCATED AT 250 WORDS)

Analgesics↗
PubMed1991

Radical proposal for the treatment of malignant astrocytoma.

The traditional treatment for anaplastic astrocytoma (AAF) and glioblastoma multiforme (GBM) leads to local relapse. The recurring element is assumed to be previously radioresistant, reorganizing hypoxic cells that require up to three times the traditional photon irradiation dose for inactivation. We are proposing to coagulate the original lesion with high-dose precision brachytherapy, immediately followed by resection to save the patient from secondary effects of the necrotic region. The treatment then continues with adjuvant external beam radiation therapy to the local surrounding brain and concomitant chemotherapy. The approach inverts the traditional regimen. It has the virtue of being precise, avoiding secondary effects of the necrotic tumor, and satisfying accepted radiobiological principles.

Astrocytoma↗
PubMed1991

The adjuvant action of cholera toxin is associated with an increased intestinal permeability for luminal antigens.

This study addresses the question of whether cholera toxin (CT) increases gut permeability for molecules greater than 3000 Da and whether such an effect is associated with an adjuvant function by CT on the gut immune response. We found that CT after oral administration gives rise to strikingly increased gut permeability for Dextran (Mw 3000) concomitantly with a strong enhancing effect on the anti-keyhole limpet hemocyanin (KLH) specific immune response in the lamina propria after oral immunization with KLH plus Dextran and CT. In contrast, the B-subunit of the holotoxin, which lacks the adenylate cyclase/cAMP-activating property of CT, failed to increase gut permeability as well as local anti-KLH immune responses. These results might suggest a causal linkage between the ability of CT to increase gut permeability and its adjuvant property on gut mucosal immune responses. In addition this finding supports the notion that the adenylate cyclase/cAMP system plays a regulatory role in gut permeability and is important in enhancing mucosal immune responses. Based on previous studies and the present data we propose that the mechanism for CT's adjuvant function on mucosal immune responses is by affecting antigen-presenting cells, T and B cells in the gut to give a net enhancing effect on the stimulation of local immunity, and that the CT-induced increase in gut permeability might be part of the adjuvant mechanism by facilitating luminal antigens to access the gut mucosal immune system.

Adenylyl Cyclases↗
PubMed1990

Enucleation after plaque radiotherapy for posterior uveal melanoma. Histopathologic findings.

A review of 1019 patients with posterior uveal melanomas, who were treated with episcleral plaque radiotherapy between April 1976 and December 1987, showed that 59 (6%) of these patients have thus far required enucleation of the affected eye. The most common clinical reasons for enucleation were tumor regrowth (51%) and neovascular glaucoma (31%). These irradiated melanomas were of mixed cell type in 40 cases (68%), spindle in 10 cases (17%), totally necrotic in 7 cases (12%), and epithelioid in 2 cases (3%). Some degree of tumor necrosis was seen in all cases. Overall, the median number of mitoses per 40 high-power fields in these irradiated tumors was 0. Most (64%) of the tumors had no identifiable mitosis in 40 high-power fields. A three-way simultaneous comparison of the following groups was made: irradiated eyes enucleated for tumor regrowth, irradiated eyes enucleated for neovascular glaucoma, and a matched group of nonirradiated posterior uveal melanomas. This comparison showed that the largest tumor dimension was significantly greater in the irradiated eyes enucleated for tumor regrowth than in the other two groups. Mitotic activity was significantly higher in the irradiated tumor regrowth and nonirradiated groups than in the irradiated neovascular group. There was no significant difference among the three groups in an analysis of height. The results suggested that mitotic activity may exist after plaque radiotherapy, especially when there is clinical evidence of tumor regrowth.

Brachytherapy↗
PubMed1989

Cellular basis of immunomodulation by cholera toxin in vitro with possible association to the adjuvant function in vivo.

Cholera toxin (CT) is a potent oral immunogen that also acts as a strong mucosal adjuvant for immune responses to related as well as unrelated Ag. To elucidate the immunomodulating effects of CT at the cellular level we have examined interactions of CT with APC and with B and T lymphocytes in vitro. CT markedly stimulated the production of IL-1 from APC (mouse peritoneal macrophages or macrophage cell line P388D1) but did not induce Ia-Ag and had marginal, if any, effect in potentiating Ia Ag expression stimulated by rIFN-gamma on these cells. CT had differential effect on T cell proliferation in vitro, usually strongly inhibitory but on Con A-stimulated spleen cells during prolonged (greater than or equal to 5 days) culture or when added on day 4 or later to these cultures up to a two- to three-fold enhancement of proliferation was seen. CT-induced inhibition of T cell proliferation was associated with decreased production of IL-2 and anergy to exogenously added IL-2 despite apparently normal expression of IL-2R. Similar to what was found with T cells LPS-stimulated spleen B cells demonstrated both inhibition and enhancement of proliferation in the presence of CT: in high concentrations (greater than or equal to 10(-8) M) and early in culture (day 3) CT had a strong inhibitory effect on the proliferation of B cells, whereas later (day 6) and/or at lower CT concentrations (10(-9) to 10(-11) M) the proliferation was increased up to 10-fold. The net effect of CT treatment on Ig-production by LPS-stimulated spleen B cells was seen as an enhanced level of IgA and IgG but not IgM in culture supernatants. The differential effects of CT on the cells of the immune system observed in vitro may, singly or in combination, explain the immunostimulatory function of CT.

Adjuvants, Immunologic↗
PubMed1989

Reasons for enucleation after plaque radiotherapy for posterior uveal melanoma. Clinical findings.

A review of 1019 patients with posterior uveal melanomas who were treated with episcleral plaque radiotherapy showed that 59 (6%) required enucleation of the affected eye. Seventeen of the enucleations were done within 1 year, 30 within 2 years, and 55 within 5 years. The enucleated eyes had been treated with a cobalt-60 plaque in 39 cases, a ruthenium-106 plaque in 13 cases, an iodine-125 plaque in four cases, and an iridium-192 plaque in three cases. The primary reasons for enucleation included tumor regrowth in 30 cases (51%), neovascular glaucoma in 18 (31%), patient request in five (8%), scleral melting in four (7%), painful bullous keratopathy in one (2%), and hemolytic glaucoma in one (2%). The time interval from plaque treatment to eventual enucleation averaged 29 months. Tumor regrowth requiring enucleation was detected clinically an average of 28 months after treatment. In these cases the average radiation dose to the tumor apex was 7700 cGy and to the tumor base 36,000 cGy. Uncontrollable neovascular glaucoma occurred an average of 38 months after plaque radiotherapy and, most commonly, after cobalt-60 plaques were used. Eyes with plaque-induced scleral melting eventually required enucleation after an average of 10 months. In all cases of scleral melting, the tumor was ciliochoroidal.

Adult↗
PubMed1989

Episcleral plaque radiotherapy for retinoblastoma.

The authors report their preliminary results of episcleral plaque radiotherapy (cobalt 60, iridium 192, ruthenium 106, and iodine 125 plaques) in 50 selected patients with retinoblastoma. There were 97 plaque applications to 51 affected eyes in these 50 patients. The plaque was used as primary treatment in 15 eyes and as secondary treatment after failure of external beam radiotherapy, photocoagulation, and/or cryotherapy in 36 eyes. Vitreous seeding of tumor cells was evident ophthalmoscopically in 49 of the 51 eyes, negating the possibility of ultimate success by further photocoagulation or cryotherapy. In 18 patients, the contralateral eye had been enucleated and the remaining eye was being considered for enucleation because all other treatment modalities had failed. In 2 of these 18 patients (11%), the remaining eye was salvaged with plaque radiotherapy and some vision was preserved. In 33 eyes with less advanced tumors, 31 had some degree of vitreous seeding by tumor cells. The eye has been retained in all 33 of these patients and useful vision preserved in most. On the basis of these preliminary observations, the authors conclude that plaque radiotherapy can be used successfully as a primary treatment for selected cases of unilateral or bilateral retinoblastoma or as a supplemental treatment after other treatment methods have failed. The current indications for plaque radiotherapy and its advantages over other therapeutic modalities are discussed.

Brachytherapy↗