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Biomedical subjects

A Persson

Publications and source records attributed to A Persson.

At least 127 records · Page 7Linked to original sources
PubMed1988

CP4: a pneumocyte-derived collagenous surfactant-associated protein. Evidence for heterogeneity of collagenous surfactant proteins.

Type II pneumocytes secrete pulmonary surfactant and are known to synthesize SP-35, a collagenous surfactant-associated protein. Freshly isolated type II cells also synthesize other bacterial collagenase-sensitive and hydroxyproline-containing proteins, including a glycoprotein designated CP4. CP4 was isolated from rat pneumocyte culture medium by immune precipitation with polyclonal antibodies to rat surfactant proteins or by DEAE chromatography and reverse-phase or gel permeation HPLC. CP4 did not cross-react with polyclonal antibodies to SP-35 and was completely resolved from SP-35 by SDS-PAGE (Mr 43K reduced) or isoelectric focusing. Unlike SP-35, which consists of acidic isoforms assembled as disulfide-bonded dimers and multimers, CP4 was secreted as basic isoforms assembled as disulfide-bonded trimers. Differences in primary structure were demonstrated by CNBr and V8 protease peptide mapping. The secretion of both proteins was inhibited by 2,2'-dipyridyl, an inhibitor of posttranslational prolyl and lysyl hydroxylation and collagen triple helix formation. CP4 was isolated from EDTA extracts of rat surfactant. These studies provide evidence for the heterogeneity of pneumocyte-derived collagenous surfactant-associated proteins.

Animals↗
PubMed1988

In-vivo demonstration of reduced benzodiazepine receptor binding in human epileptic foci.

Ten patients with partial epilepsy and five healthy controls had positron emission tomography (PET) of the brain after intravenous administration of the 11C-labelled benzodiazepine (BZ) receptor ligand 'Ro-15 1788'. In all ten patients BZ receptor binding was significantly lower in the epileptic focus than in the contralateral homotopic reference region and the remaining neocortex. No asymmetries in BZ receptor binding were observed between homotopic reference regions in the controls or the non-epileptic regions of patients. These results demonstrate the potential of the BZ receptor as a biochemical marker for display of epileptic foci by PET, and also strengthen the hypothesis that inhibitory mechanisms are disturbed in the epileptic focus.

Adult↗
PubMed1988

In vivo and in vitro receptor autoradiography of the human brain using an 11C-labelled benzodiazepine analogue.

In vitro autoradiography of an 11C-labelled ligand, Ro 15-1788, has been used to visualize benzodiazepine binding sites in large human brain cryo-sections. In parallel, using the same radioligand, an in vivo study of a human healthy volunteer was performed, by means of positron emission tomography (PET). The in vitro and in vivo mapping of the ligand demonstrated a very similar binding pattern, although the poor resolution of PET precluded a full discrimination of fine details. The 11C-autoradiograms showed good spatial resolution, even with distinction of different layers in the cerebral and cerebellar cortex. In a separate experiment, the spatial resolution of 11C-autoradiography was found to be 180 microns, using 80-microns-thick cryo-sections. It is emphasized that in vitro and in vivo studies of the same radioligand give complementary information, which is valuable in the assessment of PET images.

Aged↗
PubMed1988

PET scanning--a new tool in clinical psychopharmacology.

Quantitative methods were developed for the determination of dopamine and benzodiazepine receptor characteristics in the living human brain by positron emission tomography (PET). As ligands, the 11C-labelled analogues of the selective antagonists of dopamine receptor subtypes, SCH 23390 and raclopride, and the benzodiazepine antagonist, Ro 15-1788, were used. Tracer amounts of the ligands were injected intravenously into healthy volunteers and schizophrenic patients. The distribution of ligand indicated high densities of D1 as well as D2 dopamine receptors in the basal ganglia. Binding of [11C]-SCH 23390 was also significant in the neocortex where it was shown to represent binding to D1 as well as to 5-HT2 serotonin receptors. High densities of specific benzodiazepine receptor binding were obtained in most neocortical brain areas and in the cerebellum. Using saturation procedures, Bmax and Kd values could be obtained for D2 and benzodiazepine receptors. A comparison of D2 receptor densities in drug-naive schizophrenic patients and healthy volunteers demonstrated similar receptor characteristics in the major basal ganglia in these groups of subjects. Different chemical classes of conventional and unconventional antipsychotic drugs produced a 65%-85% occupancy of D2 receptors when given in clinical doses to schizophrenic patients. High does of diazepam produced a marked occupancy of benzodiazepine receptors during the first hours after oral administration to healthy volunteers. These in vivo methods should be valuable tools for the further analysis of the effects of drug on neuroreceptors in the living brain of neuropsychiatric patients.

Animals↗
PubMed1988

Loss of directional orientation control of lower jaw movements in persons with internal derangement of the temporomandibular joint.

Lateral mandibular movements were performed on command by 50 patients with TMJ disk displacement associated with severe pain. In 22 patients the displacement was reversible, and in 28 patients it was permanent. An additional 50 patients with disorders of the masticatory system other than disk displacement were examined, as well as a group of 50 subjects without any signs or symptoms involving the masticatory system. The results showed that 22 patients (4 with reversible and 18 with permanent disk displacement) failed to move the mandible without tooth contact toward a predetermined direction and, instead, moved it in the opposite direction. The persons themselves were convinced that the direction of movement was correct. If finger pressure was applied to the joint area on the affected side, 25% of the patients with loss of directional control were able to move correctly. A normalization of the directional control was attained in 20% of the cases if lateral movements were performed with light tooth contact. All the patients with disorders of the masticatory system other than anterior disk displacement demonstrated a correct lateral mandibular movement pattern. In the control group, 2% demonstrated incapability of directional control of lateral jaw movements. The results indicate that loss of directional control of the lower jaw is associated with disk displacement.

Cartilage, Articular↗
PubMed1988

11C-labelling of Ro 15-1788 in two different positions, and also 11C-labelling of its main metabolite Ro 15-3890, for PET studies of benzodiazepine receptors.

The benzodiazepine receptor antagonist Ro 15-1788 has been labelled with 11C in two different positions [( methyl-11C]Ro 15-1788 (I) and [ethyl-11C]Ro 15-1788 (II]. Product I was prepared by N-alkylation of the desmethyl compound (Ro 15-5528) with [11C]methyl iodide and product II was prepared by esterification of the desethyl compound (Ro 15-3890) with [11C]ethyl iodide. Ro 15-3890, the main metabolic product of Ro 15-1788, was labelled by two synthetic routes. In route A, [methyl-11C]Ro 15-3890 (III) was prepared by N-alkylation of the corresponding desmethyl compound (Ro 15-6877) with [11C]methyl iodide. In route B, III was prepared by a subsequent hydrolysis of I. The radiochemical yields were on the order of 15-60% (EOB) with an overall synthesis time of 40-50 min. Compounds I, II and III were isolated by semi-preparative HPLC and the radiochemical purity was in all cases greater than 99%.

Carbon Radioisotopes↗
PubMed1988

Induction of scoliosis in the growing rabbit by unilateral rib-growth stimulation.

Growing rabbits were subjected to surgical resection of the intercostal nerves on the right side, posteriorly or anteriorly. Two other groups of animals were used as sham and as normal controls. Six months after the nerve resection, there was no electromyographic evidence of denervation of the involved muscles. Radiologic examinations revealed progressive development of a curve, convex to the left, in each animal of the two resection groups. Analysis of structural changes by computed tomography showed rotation of the apical vertebra about the longitudinal axis. Rib cage deformity was diagnosed in 82% of the rabbits. The experimental model developed for induction of scoliosis is simple. The surgical procedure involves just one selected and easily recognized anatomic structure, leaving the vertebral structures and their vicinity intact. Reliable analysis of the underlying mechanism of the developing scoliosis is thereby assured.

Animals↗
PubMed1987

Effects of combined pancreatic and renal transplantation on diabetic neuropathy: a two-year follow-up study.

To investigate whether diabetic neuropathy can be reversed after pancreatic transplantation 13 diabetic patients were examined by means of conventional electroneurography and tests on autonomic function before and 6, 12, and 24 months after combined renal and pancreatic transplantation. 15 diabetic patients receiving a kidney graft only and 15 non-diabetic kidney graft recipients served as controls. Before transplantation neuropathy was most advanced in the two diabetic groups. Both diabetic groups showed a similar slight but significant improvement of nerve conduction after transplantation. In the non-diabetic group nerve conduction became essentially normal. No group showed improvement in autonomic dysfunction. The improvement in nerve conduction after combined kidney and pancreas transplantation was most probably due to the elimination of uraemia. Furthermore, 2 years of normoglycaemia did not reverse the diabetic neuropathy to an important extent at this late stage of the disease.

Adult↗
PubMed1987

A quantitative cerebral and whole body autoradiographic study of a intravenously administered benzodiazepine antagonist 3H-Ro 15-1788 in mice.

3H-Ro 15-1788, a benzodiazepine receptor antagonist, was injected IV into male and pregnant mice. Autoradiograms were prepared from sagittal sections of animals killed after 30 s to 48 h. In the adult animal there was a rapid and high initial accumulation of radioactivity in the brain as compared to other organs and tissues. The highest accumulation was found in cortical brain areas, such as the olfactory bulb and the frontal cortex. Cerebellar cortex, globus pallidus, amygdala, substantia nigra, colliculus, hippocampus and pons followed in rank order. The rate of decline of radioactivity was highest in the pons and lowest in the olfactory bulb. The initial disappearance of radioactivity from the cerebellum was higher than from the other brain regions. Ro 15-1788 was rapidly eliminated; 4 h after drug administration there was an almost complete clearance of radioactivity from all tissues. After 24 h no trace of activity remained in the animal. The distribution of radioactivity at later time points indicates that metabolites of Ro 15-1788 are eliminated by fecal, urinary and nasal secretion. In the fetus also there was an early accumulation of radioactivity in the central nervous system. The radioactivity in fetal organs was lower than in the mother at all time intervals.

Animals↗
PubMed1987

Residual insulin production, glycaemic control and prevalence of microvascular lesions and polyneuropathy in long-term type 1 (insulin-dependent) diabetes mellitus.

The aim of the present study was to evaluate the role of residual insulin production in long-term Type 1 (insulin-dependent) diabetes mellitus. Ninety-seven patients with a disease duration of 9-16 years and onset before the age of 30 years were studied. C-peptide excretion in 24-h urine samples was measured as an indicator of residual insulin production. Thirty-five patients (36%) excreted C-peptide (greater than or equal to 0.2 nmol); as many as possible of them were carefully matched with a non-excretor patient with regard to age at onset of diabetes and disease duration. Twenty-nine pairs were obtained, and 22 of them agreed to participate in further investigations of glycaemic control and microangiopathic lesions. The patients who excreted C-peptide had significantly lower HbA1c than the non-excretor group, 6.9 +/- 0.3% vs 7.9 +/- 0.3%, (p less than 0.025). Moderate-to-advanced background retinopathy was found in 2 patients in the excretor group and in 7 patients in the non-excretor group. Microalbuminuria [ratio of albumin: creatinine (mg/l:mmol/l) greater than or equal to 5] was found in 1 and in 5 patients, respectively, while proteinuria [ratio of protein: creatinine (mg/l:mmol/l X 10) greater than or equal to 136] was found in 0 and in 4 patients, respectively. Microalbuminuria and/or proteinuria was found in 7 of the non-excretor group as compared to 1 in the excretor group (p = 0.046).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1987

Neurotransmitter receptor imaging in Alzheimer's disease.

Recent developments in positron emission tomography and ligand binding techniques have allowed the visualization of regional metabolism and neuroreceptor distributions in the living human brain. For dopamine-D 2 and benzodiazepine receptors it has also been possible to determine neuroreceptor characteristics such as Bmax and Kd by performing in vivo saturation analysis of ligand binding to the receptors. Using 11-C raclopride and 11-C-Ro 15-1788 as ligands for dopamine-D 2 and benzodiazepine receptors respectively we have determined Bmax and Kd-values in healthy volunteers and patients with various types of neuropsychiatric disorders. These ligands were also used in order to determine the degree of receptor occupancy in psychiatric patients treated with different types of drugs interfering with these neuroreceptors. We have administered 11-C-deoxy-glucose, 11-C-raclopride and 11-C-Ro 15-1788 to patients with Alzheimer's disease in order to examine possible alterations of glucose utilization and neuroreceptor distribution and quantities in these patients. The preliminary results indicate that this approach may be useful for the analysis of degenerative alterations of neuron populations and neuroreceptor systems in Alzheimer's disease.

Alzheimer Disease↗