PubMed HealthSearch

Biomedical subjects

A Möller

Publications and source records attributed to A Möller.

At least 19 recordsLinked to original sources

Administration of tumor necrosis factor alpha (TNF alpha) inhibitors after exposure to TNF alpha prevents development of the maximal biological effect: an argument for clinical treatment with TNF alpha inhibitors.

The cytokine tumor necrosis factor alpha (TNF alpha) is involved in the pathophysiology of a wide variety of diseases. Pretreatment with anti-TNF alpha antibodies has proven its success in animal models of disease. The question, however, whether intervention with anti-TNF alpha antibodies might be useful in the clinical situation in which TNF alpha is already produced is still unanswered. We therefore studied the relation between the duration of TNF alpha/TNF receptor interaction and the extent of the induced biological effects in two different in vitro systems: (1) the slowly induced cytotoxicity of the TNF-sensitive murine cell line L929, and (2) the rapid TNF alpha-induced expression of an adhesion molecule for the polymorphonuclear cell, ELAM-1 on human endothelial cells. The TNF alpha/TNF receptor interaction was interrupted at different times after onset of stimulation, either by washing away TNF alpha or by adding TNF alpha activity-blocking monoclonal antibody. To establish an optimal effect for both TNF alpha-induced cytotoxicity on L929 cells and TNF alpha-induced expression of ELAM-1 on human endothelial cells, the TNF receptor had to be occupied by TNF alpha for at least 30-60% of the full incubation period. This observation provides an argument that clinical intervention with TNF alpha inhibitors can be advantageous, even in a situation in which TNF alpha has already been released into the circulation.

Animals

T lymphocytes from patients with primary biliary cirrhosis produce reduced amounts of lymphotoxin, tumor necrosis factor and interferon-gamma upon mitogen stimulation.

Primary biliary cirrhosis (PBC) is considered an autoimmune disease characterized by destruction of small intrahepatic bile ducts by lymphocytes. Altered functions of these lymphocytes might reflect an abnormal immune response leading to tissue damage. We investigated lymphokine secretion by mitogen-stimulated T lymphocytes from the liver biopsies of patients with PBC and for comparison also peripheral blood. In PBC, diminished synthesis of lymphotoxin (TNF beta), tumor necrosis factor (TNF alpha) and interferon-gamma (IFN gamma) was found both in T-cell lines from liver tissue and in peripheral blood. The reduction was most prominent for TNF beta in early histological stages of PBC, and appeared to be a stable phenomenon when T cells were tested after long-term tissue culture. Analysis of mRNA levels indicates a possible link between reduced TNF beta production and a defect in interleukin-2 transcription. The data suggest that diminished lymphokine production in patients with PBC may play an important role in the immunopathogenesis of this disease.

Adult

The predominant microflora of the palatal mucosa in an elderly island population.

The prevalence and microbiology of macrophotographically documented denture stomatitis were studied in denture wearers participating in an interdisciplinary health-monitoring project (Koster Health Project) on the Koster islands, Sweden. Upper dentures were used by 26.6% of the adult population, and 59.2% of the denture wearers had stomatitis. Denture stomatitis type I was identified as sialadenitis. The more severe forms of denture stomatitis (types II and III) demonstrated increased recovery of microorganisms in the palatal mucosa in addition to sialadenitis. Only one proband showed increased growth of fungi. Hemophilus spp. and Bacteroides spp. were the predominating microorganisms in stomatitis types II and III. Shifts in the normal oral flora are suggested to be an important factor for the development of denture stomatitis. It is concluded that bacterial colonization on the palatal mucosa may play an important role in denture stomatitis in this relatively healthy population.

Aged

In vitro generation of smooth muscle-contracting leukotrienes from isolated epidermal cells.

Single-cell suspensions of murine and human epidermal cells were studied for the presence of peptidoleukotrienes (LTs), using in vitro guinea pig ileum contraction as bioassay and a commercial radioimmunoassay. The calcium ionophore A23187 at 5 x 10(-6) M alone or in combination with arachidonic acid at 10(-4) M caused release of LTC4/D4 within 10-30 min and for up to 18 h. LTB4, as was measured in the chemotaxis assay, was released at different levels and with different kinetics from the same cells. Epidermal cells may thus regulate cutaneous inflammation by secreting potent vasoactive and muscle-contracting in addition to chemotactic lipid mediators.

Animals

Mast cells and their mediators in immediate and delayed immune reactions.

Tissue mast cells and the closely related blood basophils are distinguished by their special mediators and their high-affinity IgE membrane receptors. These properties have made the cells be viewed traditionally as effector cells of immediate-type hypersensitivity reactions. More recently, mast cells have been shown to develop from the myeloid series of the bone marrow under the influence of interleukins 3, 4, 6, 9, 10 and 11. Mast cell and basophil lines of murine and human origin have also been shown to express and release interleukins 1, 3, 4, 5, 6, 8, tumor necrosis factor-alpha, granulocyte-macrophage colony-stimulizing factor and interferon-gamma. Certain cytokines are also able to induce mediator release from mast cells. Furthermore, mast cells have in the past been shown to be modestly phagocytic and to express major histocompatibility complex class II membrane markers after appropriate stimulation. These findings show that mast cells are intricately associated with immune reactions and suggest that they may not only sustain and modulate but possibly also initiate immune responses.

Animals

Monoclonal antibodies to human tumor necrosis factor alpha: in vitro and in vivo application.

Three stable murine hybridoma cell lines, which secrete monoclonal antibodies (mAb) to human tumor necrosis factor alpha (TNF alpha), were established. None of the monoclonal antibodies cross-reacted with lymphotoxin, interleukin 2 (IL 2) or Interferon gamma (IFN gamma). The highly species-specific monoclonal antibody, designated as mAb 195, neutralizes the cytotoxic activity of human and chimpanzee TNF alpha. This antibody was further used during in vivo studies to neutralize human TNF alpha in a murine animal model. The mAb 114 is a weakly neutralizing antibody that binds to a different epitope of TNF alpha than mAb 195. mAb 114 shows a wide range of cross-reactivity with TNF alpha of the following species: dog, pig, cynomolgus, rhesus, baboon and chimpanzee. The mAb 199 binds to human TNF alpha, but does not neutralize the cytotoxic activity. The epitope recognized by this mAb is in close proximity to mAb 114. A reproducible, sensitive immunoassay for human TNF7 alpha has been developed using the antibodies mAb 199 and mAb 195. The test is performed within 6 hr and detects TNF7 alpha in serum samples, with a limit of detection of 5 to 10 pg/mL.

Animals

Evaluation of the internal auditory meatus with acoustic neuromas using computed tomography.

Forty-seven patients with 48 unoperated acoustic neuromas have been studied by computed tomography (CT) with respect to bone changes. CT and conventional X-ray examination of the skull were compared. The importance of using a small collimator, proper selection of the plane of the CT section and changing of the window level is stressed. CT detects porus changes as accurately as conventional X-ray methods.

Adult

Evidence from ultraviolet absorbance measurements for a codon-induced conformational change in lysine tRNA from Escherichia coli.

From experiments with equilibrium dialysis it was concluded earlier that formation of the codon-anticodon complex triggers a conformational change in the tertiary structure of tRNAPhe from Escherichia coli. A similar conformational transition is demonstrated here in the poly(A)/tRNALys system. C-G-A or C-G-A-A was used as a probe for the conformational transition in tRNA. These probes bound to tRNAPhe and tRNALys more strongly in the presence of the corresponding codons than in the absence. In order to verify these data by an independent method, the decrease in absorbance at 300 nm that occurs on formation of the codon-anticodon complex in tRNALys (which contains 2-thio-5-methylaminomethyluridine, s2mam5U) was used. The binding constants for formation of A3 . tRNALys (Ka = 2.4 . 10(4) M-1) and A4 . tRNALys (Ka = 2.5 . 10(5) M-1) are very close to those obtained by equilibrium dialysis. In the presence of C-G-A the apparent binding constant of A3 to tRNA was raised 10-fold to 2.5 . 10(-5) M-1. It was calculated that the constant for the binding of C-G-A to the binary complex A3 . tRNALys is approximately 2 . 10(4) M-1, whereas binding to the free tRNA is lower than 10(3) M-1. Under appropriate conditions binding of A3 to tRNALys can be induced directly by the addition of C-G-A. These data demonstrate that codon-anticodon complex formation induces a conformational change in the tRNA that as a consequence allows the binding of a trinucleoside diphosphate, presumably to the T-psi-G region.

Anticodon

Computed tomography of isoattenuating subdural hematomas.

CT scans of 87 patients with subdural hematoma were compared to those of 393 patients with midline shift caused by other intracranial lesions with regard to attenuation changes in the lesion and the character of the ventricular deformity. Isoattenuating was exhibited by 25% of the subdural hematomas and 5% of the other lesions. In 70 to 80% of the isoattenuating hematomas, the diagnosis could be made on the basis of the characteristic ventricular deformity. Other diagnostic procedures are not necessary in these cases.

Brain

Chronic non-scarring folliculitis of the scalp.

Forty patients with recurrent follicular pustules of the scalp but without obvious necrosis or residual scarring were re-examined (mean 8.3 years after onset of lesions). The most common age at onset was 20-40 years. The sex ratio (M/F) was 3 : 1. Only 7 of 40 patients had concomitant acne vulgaris on the face. All patients still had active, recurring scalp lesions, although 7 out of 40 had had temporary remissions. Post-lesional scarring was not observed. Oral low-dose tetracyclines had a symptomatic effect in 7 of 11 patients. Most of the patients treated topically with steroids and alcoholic lotions experienced little or no effect. Histopathology disclosed a neutrophilic folliculitis. Bacteriological examinations showed only the usual resident microflora of the scalp with P. acnes being the most frequent species. In 3 cases (5 examined pustules), P acnes was isolated from the content of the pustules without being found on the skin surface over the pustule. Chronic non-scarring folliculitis of the scalp probably constitutes a disease entity.

Adolescent

Diagnosis of acoustic neuroma with computed tomography.

Sixty-one acoustic neuromas were examined with computed tomography (CT). For differential diagnosis the tumors were thoroughly analyzed for manner of growth, shape, volume, calcification, attenuation pattern, constrast enhancement, presence of peripheral edema, and cisternal deformation.

Adolescent

Early contrast enhancement of acoustic neuroma.

The changes of the enhancement of the lesion with time after intravenous administration of contrast medium were measured with computed tomography (CT) in 23 cases of acoustic neuroma. The pattern of high initial enhancement followed by a fairly rapid decrease is confirmed. A more rigorous study of the enhancement pattern using a mathematical description of the enhancement curve of the tumor as well as a measurement of the individual blood enhancement curve is discussed.

Adult

Changes of internal auditory meatus.

Forty-seven patients with 48 nonoperated acoustic neuromas have been studied by computed tomography (CT) with respect to bone changes. CT and conventional X-ray examination of the skull were compared. The importance of using a small collimator, proper selection of the plane of the CT section, and changing of the window level is stressed. CT detects porus changes as accurately as conventional X-ray methods.

Humans

Postmortem radiography of the subarachnoid cisterns.

A technique has been developed for stereotactic postmortem cisternography using water-soluble contrast medium and plastic material with enhanced attenuation by the addition of red lead. The latter technique can be used for the preparation of plastic casts of the cisterns, accessible for analysis by radiologic means as well as by direct inspection.

Autopsy