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Biomedical subjects

B Larsen

Publications and source records attributed to B Larsen.

At least 217 records · Page 12Linked to original sources

Immunoglobulin concentration and Gm allotypes in a family with thirty-three cases of myotonic dystrophy.

Serum IgG, IgA, and IgM concentrations were measued in 120 members of a family with 33 cases of Dystrophia myotonica (Dm) and 27 members who were "possibly affected". The Dm individuals had significantly lower serum concentrations of IgG and IgA (P<0.01), while the "possibly affected" did not differ from the matched pair controls. IgG subclass concentrations were measured and GM and Am types determined. The lower concentration of IgA in the affected individuals was not associated with a particular Am type. The concentration of IgG3 was barely lower in the effected than in the controls (P=0.05), but there were no differences for IgG1. When IgG3 concentratin was compared according to Gm haplotype, only the two affected individuals who were Gm gg had a statistically significant lower concentration than the 12 controls (P<0.02). Thus, there is no evidence that a particular subclass of IgG is being hypercatabolized in our Dm patients. A rare Gm haplotype, Gm(-, n, b) had entered the family with two brothers; it is not known whether this codes for an IgG1-IgG3 hybrid molecule or a normal IgG1 molecule with an unknown Gm allele or a gamma 1 deleted Gm haplotype.

Adolescent↗

Polyglandular autoimmune disease and HLA.

We have studied 25 patients with polyglandular autoimmune disease with respect to HLA antigens. Whereas the combination of insulin dependent diabetes with Graves' disease or atrophic thyroiditis was associated with an increase in HLA-B8, this was not found to be the case for patients with I.D.D.M. and goitrous thyroiditis. However 4/7 of these patients were DRw3 positive in contrast to previously established normal distribution of HLA-B8 in patients with goitrous thyroiditis alone. These data suggest that patients with polyglandular failure may be highly selected for HLA-B8/DRw3 positivity. We also report on two families with polyglandular autoimmune disease; the results suggest that these disorders are not necessarily transmitted with B8/DRw3 bearing haplotypes. In one family both the affected mother and non-affected father were B8 positive. The mother's B8, which was associated with DRw7, BfF and Rga did not appear to be involved in the transmission of disease susceptibility to two affected offspring. The search for complete haplotypic arrangement should be pursued to see whether this uncommon haplotype arrangement is peculiar to autoimmune diseases.

Adult↗

Effects of polycationic compounds on mitogen stimulation.

The effects of polycations added to phytomitogen stimulated human lymphocyte cultures have been studied. Within certain dose ranges all polycations tested gave rise to augmented thymidine uptake in mitogen stimulated cultures. The optimum enhancing concentrations of polycations was depending on the serum concentration in the culture medium. This was found to be due to two types of interactions: (a) Interference with mitogen binding serum factors, (b) Reaction with immunosuppressive serum proteins. Suggestive evidence for an affect of polycations also directly on the cells was found by pretreatment and cell density experiments. The direct effect on cells was found not to be due to monocyte bypass or to activation of non-T cells by the mitogen. It is pointed out that effect of chemicals on in vitro immunresponses have to be considered in relation to the charge properties of the compound.

Cell Survival↗

Supplementary motor area and other cortical areas in organization of voluntary movements in man.

1. Previous studies in man have revealed a coupling between the regional cerebral blood flow (rCBF) and the regional cerebral metabolic rate for oxygen. In normal man, increases in the regional cerebral metabolic rate for oxygen leads to proportional increases in the rCBF(34). We have measured the rCBF as an expression of the level of cortical activity simultaneously from 254 cortical regions in 28 patients with no major neurological defects, during rest and during planning and execution of a few types of learned voluntary movements with the hand. 2. We found that the rCBF increases exclusively in the supplementary motor area while subjects were programming a sequence of fast isolated movements of individual fingers, without actually executing it. 3. During execution of the same motor sequence, there were equivalent increases of the rCBF in both supplementary motor areas, but only in the contralateral primary motor area. In addition, there were more modest rCBF increases in the contralateral sensory hand area, the convexity part of the premotor area, and bilaterally in the inferior frontal region. 4. Repetitive fast flexions of the same finger or a sustained isometric muscular contraction raise the blood flow in the contralateral primary motor and sensory hand area. 5. A pure somatosensory discrimination of the shapes of objects, without any concomitant voluntary movements, also leaves the supplementary motor areas silent. 6. We conclude that the primary motor area and the part of the motor system it projects to by itself can control ongoing simple ballistic movements with the self-same body part. A sequence of different isolated finger movements requires programming in the supplementary motor areas. We suggest that the supplementary motor areas are programming areas for motor subroutines and that these areas form a queue of time-ordered motor commands before voluntary movement are executed by way of the primary motor area.

Adolescent↗

Different cortical areas in man in organization of voluntary movements in extrapersonal space.

1. This paper reports regional cerebral blood flow (rCBF) measurements in 254 cortical regions with 133Xe injected into the internal carotid artery in 19 patients, none of whom had any major neurological defect. The purpose was to demonstrate the pattern of cortical activity, as revealed by rCBF increases, during two types of unilateral voluntary movement in extrapersonal space: a) the maze test, series of fast isolated movements in various directions in a frame, executed under verbal command; and b) the drawing of a spiral in the air. 2. Both types of movements were associated with increases of rCBF in the supplementary motor area (bilaterally), the convexity part of the premotor area (bilaterally), the primary sensorimotor hand and arm area (contralaterally), and in the superior and inferior parietal region (bilaterally). 3. During the maze test there were, in addition, bilateral focal increases of the blood flow in the auditory areas, the inferior frontal regions, and the frontal eye fields. 4. It is concluded that the supplementary motor areas, which are also active during programming and execution of movement sequences in intrapersonal space (33), elaborate programs for motor subroutines necessary in skilled voluntary motion. The convexity parts of the premotor areas are activated when a new motor program is established or a previously learned motor program is modulated. The primary motor area is the exclusive executive locus for voluntary movements of the hand and arm. 5. Voluntary movements in extrapersonal space only are associated with activation of the parietal regions. These areas are assumed to provide information to the motor programming neurons about the demanded direction of motion in extrapersonal space in relation to proprioceptive reference systems. 6. The increase of rCBF in the auditory areas, the inferior frontal regions, and the frontal eye fields during the maze test were ascribed to the processing of auditory information. 7. Both tests are accompanied by a diffuse increase of the hemispheric blood flow (approximately 10%), which is assumed to be a parallel to the commonly known desynchronization of the EEG during mental work.

Adolescent↗

Cortical activity in the left and right hemispheres during language-related brain functions.

The blood flow to a given brain region increases as the level of neural activity is augmented. Hence mapping of variations in regional cerebral blood flow affords a means of imaging the activity of various brain regions during various types of brain work. The paper summarizes the patterns of cortical activity seen during various language functions, emphasizing the practically symmetrical involvement in both hemispheres. A case of auditive agnosia (with complete cortical word deafness but preserved pure tone thresholds) is presented. The patient's normal speech constitutes evidence that auditory feedback (absent in his case) is not a prerequisite for speaking.

Agnosia↗

Properdin factor B(Bf) allele BfF1 specifies an HLA-B18 diabetogenic haplotype.

We found the rare properdin factor B(Bf) variant F1 to be present in 11% of 72 patients suffering from insulin-dependent diabetes (IDDM) compared with 2% among 150 normal controls. BfF1 thus confers a relative risk for IDDM of 5.55. All eight patients and three controls who were BfF1 positive were also HLA-B18 positive, reflecting the strong linkage disequilibrium between these two factors. We suggest that BfF1 marks a 'diabetogenic' B18-bearing HLA haplotype. Studies of unselected families with one or more affected members suggest that the B18, BfF1 does not necessarily segregate with IDDM phenotype. This study provides further evidence for the genetic heterogeneity of IDDM.

Alleles↗

Middle components of the auditory evoked response in bilateral temporal lobe lesions. Report on a patient with auditory agnosia.

An investigation of the middle components of the auditory evoked response (10--50 msec post-stimulus) in a patient with auditory agnosia is reported. Bilateral temporal lobe infarctions were proved by means of brain scintigraphy, CAT scanning, and regional cerebral blood flow measurements. The middle components were found to be normal regarding latency (pa approximately 30 msec) and configuration of the recordings, when evaluated relative to the peripheral hearing loss in the patient and to the corresponding normative template. Based upon the combined procedures, it is concluded that the middle components cannot be generated exclusively, if at all, in the primary auditory cortex, located in the temporal lobe. Furthermore, the responses are found to be of neurogenic origin according to the methodological procedure applied.

Aged↗

HLA haplotypes in familial Graves' disease.

In order to further elucidate the genetics of Graves' disease, we studied two families with several affected members, as well as tested the degree to which HLA haplotypes were shared in affected sibpairs. Further, we sought to identify the disease related haplotypes by determining the haplotypes shared among affected parent-child combinations. In one family, two affected sibs differed at four possible parental HLA haplotypes; no evidence of recombination was observed which could account for the result. In the other family, five siblings were affected. Four out of the five affected sibs shared the maternal haplotype HLA-A11, Bw51, Cw5, Cw-, DRw5, Bfs, GLO1, whereas three shared the paternal haplotype HLA-A1, B8, Cw-, DRw3, BfS and GLO1. Looking at haplotype sharing, two pairs of sibs were found to be HLA identical, whereas the fifth sib shared one haplotype with one of these pairs but not with the other. Out of 14 (eight of our own and six from the literature) affected sibpairs examined, nine were found to be HLA identical and four shared one haplotype, suggesting that the contribution of both paternal haplotypes may be necessary for the susceptibility to the disease. Fourteen parent-child combinations were studied; in only three out of 13 in which the shared haplotype could be ascertained was the haplotype B8 positive; this distribution is similar to controls. However, of the remaining 10 combinations which did not share a B8 positive haplotype, five were B8 positive at one or the other of the non-shared haplotypes.

Cytotoxicity Tests, Immunologic↗

Activation of the supplementary motor area during voluntary movement in man suggests it works as a supramotor area.

Measurements of cerebral blood flow in man revealed that complex voluntary movements are associated with a blood flow increase in the supplementary motor area of the brain. This increase is additional to and similar in magnitude to the Rolandic sensorimotor area activation that occurs during all kinds of movement. When subjects counted silently there was no activation of any focal cortical area in the brain; when they counted aloud there was a marked increase in activity in the supplementary motor area. These results are consistent with the hypothesis that the supplementary motor area plays a major role in the initiation and control of at least some kinds of voluntary movement in man and is, therefore, a motor center of a higher order than the primary Rolandic areas.

Cerebrovascular Circulation↗

Bacterial growth inhibition by amniotic fluid. VIII. Evaluation of a radiometric bioassay for rapid, in vitro demonstration of phosphate-sensitive bacterial growth inhibitor in amniotic fluid.

A radiometric bioassay based on the continuous monitoring of 14CO2 released from labeled glucose in the presence of amniotic fluid or amniotic fluid with added phosphate has been employed to detect the presence of a phosphate-sensitive bacterial inhibitor in amniotic fluid near term. The time required for detection of the inhibitory activity is approximately 12 hours, in contrast to approximately 36 hours required for a previously reported technique. Application of this radiometric bioassay to demonstrate bacterial growth inhibition by amniotic fluid and physicochemical properties of the inhibitory activity yielded results comparable to those obtained with the older method of plate counts of viable bacteria. By the new technique it was possible to demonstrate that the inhibitory activity was phosephate sensitive, heat stable, inactivated by metal chelation, removed by bentonite, and present in a low-molecular-weight fraction of amniotic fluid.

Amniotic Fluid↗

Cortical activation pattern during saccadic eye movements in humans: localization by focal cerebral blood flow increases.

Regional cerebral blood flow (rCBF) was measured in human subjects during saccadic eye movements by a 254-channel dynamic gamma camera. Focal rCBF increases were repeatedly observed in an area within the middle precentral and premotor regions which corresponds to the frontal eye field in humans. Our findings suggest that this region is localized between the "face" and "hand" areas in the precentral gyrus and extends anteriorly out of the primary motor strip into the adjacent premotor zone. In addition, saccades were associated with focal blood flow increases in regions corresponding to the frontal supplementary motor area and to the posterior temporooccipital visual association cortex. Similar changes in patterns of rCBF occurred during contralateral and ipsilateral horizontal saccades and also during vertical saccades, and did not differ between the right and left hemispheres. Focal rCBF increases were observed in the frontal eye field during several additional test procedures including ocular fixation and visual perception of a nonmoving target, auditory stimulation with closed eyes, and reading. It is presumed that these focal flow increases reflect increased localized neuronal activity and metabolic rate and therefore permit visualization of the cortical activation pattern associated with saccadic eye movements in humans.

Cerebral Cortex↗

Additions to the myotonic dystrophy linkage group.

One hundred and thirty members of a family with 33 cases of Dystrophia myotonica (Dm) were tested for various genetic markers including Km, Jk, Lu and Se. All individuals tested were Lua negative, but many were heterozygous for the other markers. Except for two cases all patients with Dm were positive for Km3 and Jka and they were secretors. Assuming the genes are linked and that the order of the loci is Km, Jk, Lu, Se, Dm, then there were 22 meioses informative for Dm and in 10 of these a recombination must have occurred between two of the five loci. Looking at individual pairs of loci, there were no recombinations between Km and Jk in seven informative meioses, three recombinations out of 10 meioses informative for Jk/Se, no recombinations between Se and Dm in five informative meioses and three recombinations out of 12 meioses informative for Jk/Dm.

Female↗

The separation of peptide hormone diastereoisomers by reverse phase high pressure liquid chromatography. Factors affecting separation of oxytocin and its diastereoisomers--structural implications.

Experimental conditions and parameters involved in high performance liquid chromatography (HPLC) separations of the peptide hormone oxytocin and seven of its diastereoisomers, namely [1-hemi-D-cystine]-, [2-D-tyrosine]-, [4-D-glutamine]-, [5-D-asparagine]-, [6-hemi-D-cystine-], [7-D-proline]-, and [8-D-leucine]-oxytocin, on reverse phase columns were investigated. The effects of solvent, pH, and salt concentration were studied. Using the solvent systems 10% tetrahydrofuran-ammonium acetate buffer or 18% acetonitrile-ammonium acetate buffer and the muBondapak C18 support, oxytocin was separated from each of its diastereoisomers under all conditions studied, but the order of elution of diastereoisomers was highly dependent on solvent and to a lesser extent on pH. Separations of the hormone and its diastereoisomers on reverse phase HPLC and on classical partition chromatography on Sephadex G-25 were compared. The results are discussed in terms of the interactions of the solute with the reverse phase column and the solvent system. Implications of these findings in terms of the different solution conformations of the peptides are discussed.

Amino Acid Sequence↗

Regional blood flow in canine myocardium as determined by local washout of a freely diffusable radioactive indicator.

The aim of this study has been to examine the utility of the washout of a freely diffusable radioactive indicator as a measure of regional myocardial blood flow in open-chest anesthetized dogs. The method employed was direct intramyocardial injection of Xenon-133 followed by measurement of its gamma-radiation. The experimental washout curves show, after a short acceleration period, monoexponential washout of the indicator over two decades. We found indications of insignificant veno-arterial shunting by diffusion of the blood flow level measured, insignificant arterial recirculation of the indicator, and minimal radioactive contribution to precordial residue versus time curves arising from right heart or non-myocardial tissue. We suggest that diffusion equilibrium between the tissue in the counting field and the blood leaving it is maintained during the linear down slope of two decades of the clearance curve, and that local blood flow can be calculated from washout rate constant obtained from this part of the curve. The method employing intramyocardial injection of Xenon-133 was found to give the same results as atraumatic epicardial labelling indicating negligible effect of the injection trauma and supporting the validity of the local injection method using small volumes (2-10 microliter).

Animals↗

A study of human leukocyte D locus related antigens in Graves' disease.

An association between Graves' disease and the human leukocyte antigen (HLA) system has previously been reported. The disease was more strongly associated with the HLA D locus antigen Dw3 than with HLA B8. Products of the HLA D locus are determined by the interaction of test cells with standard typing lymphocytes, a technically difficult procedure. Recently, it has been possible to type serologically for D locus related (DRw) specificities on peripheral bone marrow-derived (B) lymphocytes. Blood B lymphocytes from 50 unrelated controls and 41 patients with Graves' disease were typed for seven HLA DRw specificities. 28 patients with Graves' disease (68%) were positive for DRw3, in contrast to 14 controls (28%); whereas only 21 patients (50%) were HLA B8 positive, compared with 13 (26%) controls. Thus, positivity for DRw3 afforded a relative risk for Graves' disease of 5.5, whereas that for HLA B8 amounted to 3.0. Additionally, a family with multiple cases of Graves' disease in which the disease was previously shown to be inherited with the haplotype, was linked to DRw2, which suggests that the susceptibility to the disease was inherited in association with that antigen. Two HLA B/glyoxalase recombination events were observed in this family; in both instances HLA DRw followed HLA B. This study thus demonstrates that the disease susceptibility gene for Graves' disease is in strong linkage disequilibrium with DRw3; however, it may be associated with other DRw specificities and inherited within family units in association with them.

Alleles↗

On the pathogenesis of bedsores. Skin blood flow cessation by external pressure on the back.

This paper is devoted to elucidation of the question: Which external pressure is required to stop skin blood flow at the skin - support interface in humans lying on the back in the supine position? Cessation of blood flow was recorded as cessation of washout of an intracutaneous depot of 131I-antipyrine mixed with histamine. The external pressure was measured by a small airfilled plastic cushion connected to a mercury manometer. In 11 normal subjects, eight patients with hypertension and seven patients with tetra- or paraplegia the "flow cessation external pressure" (FCEP) was strongly correlated to the auscultatory brachial mean blood pressure (p less than or equal to 0.001). The difference mean blood pressure - FCEP was on average 4 mmHg (range (-11) - (+20) mmHg) and there was no significant difference between the three groups studied. Thus external pressure exceeding the actual mean blood pressure will stop skin circulation.

Adult↗