The peak of electromechanical experimentation in physiology: a unique view through Walter Miles' "Report of a Visit to Foreign Laboratories" in 1920.
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Europe↗
Biomedical subjects
J Braun
Publications and source records attributed to J Braun.
[The rate of injection of succinylcholine and onset of neuromuscular action, serum potassium or myoglobin levels. Studies in men during halothane anesthesia].
Succinylcholine was injected at different speeds to 60 men in halothane anesthesia, to see whether the rate of injection influenced the effects. METHODS. Sixty men (ASA I and II, mean age 28.6 years) undergoing surgery without muscle trauma were studied. They were treated uniformly with respect to premedication, anesthesia, venipuncture (cubital), and concentration (1%) and dosage (1 mg/kg) of succinylcholine (SCh). The only difference lay in the speed of injection of the relaxant: 20 mg/s, 8 mg/s, 4 mg/s, 2 mg/s and 1 mg/s, 12 patients being randomly allocated to each. The injection rate was controlled by a preprogrammed microprocessor pump system (XD 5500, HC Ulrich, D-7900 Ulm, Donau). The neuromuscular transmission was monitored by the adductor pollicis twitch technique using indirect supramaximal stimulation (Accelograph, biometer, DK-5120 Odense). The recorded twitch response allowed determination of the total onset time (TOT) from the beginning of the injection to the maximal twitch depression, its components, latent and manifest onset times (LOT and MOT), and the twitch depression factor ki. Blood samples for measurement of potassium and myoglobin levels (RIA, sensitive to 5 ng/ml) were taken before and 5, 15, and 30 min after SCh administration. For determination of the course (difference between two values before and after SCh), the maximum level up to 30 min was recorded. RESULTS. The twitch depression amounted to 100% in 57 patients and to 93% or 98% in the remaining 3. Reducing the speed of injection led to significant prolongation of TOT and LOT (Table 3) and significant differences in the onset characteristic in regard to twitch depression factor ki (Table 4). No significant influence on the increase in potassium (Table 7) and myoglobin (Table 8) was observed. CONCLUSION. These findings give no cause to inject SCh more slowly than usual in healthy adults.
Adult↗
Unique V gene usage by B-Ly1 cell lines, and a discordance between isotype switch commitment and variable region hypermutation.
We have previously described a series of Ly-1+ B cell lines obtained as spontaneous outgrowth cultures from mouse spleen cells (B-Ly1 cells). In this study, we report the variable region sequences utilized by independent cell lines derived from three mouse strains. Remarkably, V region utilization and junctional diversification were essentially identical in all three cell lines. These included: lambda 1 light chain; JH1; DSP2-7,8; and, a novel VH gene segement. The VH was highly homologous to CP4, a rare VH family previously found in a group of Ly-1 B cell-derived autoantibodies to bromelain-treated mouse red blood cells. The selective expression of this unusual lg species implies the action of distinctive molecular or immunophysiological processes in the outgrowth of B-Ly1 cell lines. Clarification of these factors may be relevant to understanding the peculiar biology of Ly-1 B cells in vivo. We have also evaluated switch-committed B-Ly1 clones to determine whether this phenotype is accompanied by variable region somatic mutation. However, no evidence for somatic mutation was observed in these induced clones. This may indicate that these two processes are independently regulated, despite their common concordance in vivo.
Amino Acid Sequence↗
[Diagnosis of kidney transplant rejection. The value of scintigraphy, sonography and NMR tomography].
Scintigraphy, ultrasound and magnetic resonance imaging were undertaken within three days on 73 patients who had had renal transplantation. Clinical and histological criteria were used to assess the ability of diagnosing rejection of the transplant. In all instances of rejection cortex-marrow differentiation was absent on magnetic resonance (MR) imaging; there were no false-negative results. Sensitivity as to rejection was 100% for MR imaging, 58% for scintigraphy and 32% for ultrasound. It may be possible to distinguish between cytomegalovirus infection and rejection reaction by MR imaging. It is concluded that MR imaging is the most reliable method for predicting rejection reactions, while ultrasound and scintigraphy are valuable for making other diagnostic decisions.
Evaluation Studies as Topic↗
[Risks of analgetics administration. Observations on 2 extensive epidemiological studies].
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Agranulocytosis↗
[Influence of polymerization of D-amino acid oxidase on the behavior of the enzyme immobilized on chitosan by covalent fixation].
D-Amino-acid oxidase is a flavoprotein using FAD as cofactor. The enzyme has been immobilized in the presence of FAD on a non-porous matrix: chitosan. This support is covalently bound to the enzyme with glutaraldehyde as cross-linking reagent. It is characterized by a good mechanical resistance to mechanical stirring. The enzymatic assays have been performed in batch reactor with D-phenylglycine as substrate by a spectrophotometric method which is based on the variation of the absorbance at 252 or 280 nm. The behaviour of the biocatalysts has been studied during repeated assays of 1 h at 25 degrees C in the absence of exogenous FAD. The experimental results have been compared with those obtained with the soluble enzyme tested in the presence or in the absence of FAD. The dependence of D-amino-acid oxidase on FAD concentration has been studied. Immobilized enzyme on chitosan appears to be less sensitive to the association-dissociation equilibrium of FAD. This property and the capacity of the enzyme to polymerize spontaneously in solution according to the experimental conditions have been established. The fact that the enzyme can exist in various oligomeric forms is of major importance because its catalytic expression is dependent of this phenomenon. The polymerization is known to be responsible for a decrease of the maximal rate V of the enzyme. It has also been shown that in the same way this decrease was accompanied by an improvement of the affinity of enzyme for substrates. Furthermore, the value of the dissociation constant of the apoenzyme-FAD complex is significantly smaller as the degree of polymerization is high. The conclusion is that the dissociation of the cofactor can be avoided if the immobilization step is carried out at high concentration of enzyme which is favourable to its polymerization.
Chitin↗
Cystic meningiomas.
Four cases of cystic meningiomas were found among 194 meningiomas diagnosed by computed tomography (CT) and operated on during a 7 year period, an incidence of 2%. The cysts were in all cases peritumoral. The cyst's wall was the brain itself, and the ependymal ventricular wall was part of their medial boundary. They contained xanthochromic fluid with a high protein content. Three meningiomas were parasagittal and one was adjacent to the pteryon and the external part of the sphenoid ridge. The mural nodules were in 2 cases apparent single nodes although in one it was part of multiple distant and regional growths, in another the tumour was built by the aggregation of 2 nodes, the remaining case was an "en plaque" meningioma. All were definitely attached to the dura. Histological pattern was different in every case. Those parasagittal were: one pure meningotheliomatous, one mixed meningotheliomatous with pseudo psammomatous and lipoblastic sections and one highly vascular angioblastic; the pteryonal case was psammomatous and microcystic. CT diagnosis is difficult because glial, metastatic and other tumours may look cystic and resemble cystic meningiomas. Nevertheless in 3 cases the correct diagnosis was suspected preoperatively because the solid portion of the tumour showed intense and homogeneous contrast enhancement with a sharp edge and was located adjacent to the dura. On the other hand in the remaining case, the parasagittal solid tumour was not readily apparent on CT (the "en plaque", case), and the tentative preoperative diagnosis was of an epidermoid tumour.(ABSTRACT TRUNCATED AT 250 WORDS)
Brain Diseases↗
Does alpha 1-acid glycoprotein reduce the unbound metabolic clearance of disopyramide in patients with renal impairment?
The pharmacokinetics of disopyramide was studied in 15 patients with renal dysfunction (4 with pyelonephritis, 7 with glomerular nephritis and 4 with interstitial nephritis). The elimination rate constant of unbound disopyramide was 0.094 h-1 and CLu/f (unbound clearance divided by bioavailability) was 245 ml/min. Both the unbound renal clearance (CLR) and CLu/f were highly correlated with the creatinine clearance (CLCR). The apparent unbound metabolic clearance in the patients was approximately two-fold lower than that previously reported in normal subjects. The estimated unbound metabolic clearance in the renal dysfunction patients showed a significant negative correlation with the alpha 1-acid glycoprotein (AAG) concentration and only a weak, non-significant correlation with CLCR. As AAG in the renal dysfunction subjects was increased in comparison with normal values, it is possible that AAG is a factor in the decrease in the apparent unbound metabolic clearance.
Adult↗
[Manometric and electrophysiologic study procedures for the functional diagnosis of the internal anal sphincter].
In 49 subjects, simultaneous manometric and electrical investigations of the internal anal sphincter were performed. In resting state slow potentials were recorded in all subjects at a mean frequency of 20.6 +/- 0.6 cpm for needle electrodes and 16.0 +/- 0.5 cpm for surface electrodes in bipolar technique. The mean amplitude amounted to 380.6 +/- 28.4 microV respectively 411.6 +/- 27.8 microV for both electrical derivations. Whereas frequency was fairly constant, amplitude of slow potentials changed interindividually and intraindividually. Anal sphincter pressure did not correlate with amplitude and frequency of slow potentials. Sphincter relaxation by rectal distension was associated with inhibition of slow potentials. Both, percentage of inhibition of slow potentials and of sphincter relaxation were proportional to the volume of rectal distension. There was also a direct correlation between volume of rectal distension, depth of sphincter relaxation and length of inhibition of slow potentials. When 10 ml, 25 ml and 50 ml of air were used for rectal distension, duration of inhibition of slow potentials were 8.5 +/- 1.5 s, 12.5 +/- 1.6 s and 15.1 +/- 1.2 s (p less than 0.05) for bipolar tracings, depth of relaxation respectively 15.0 +/- 1.2 mmHg, 26.1 +/- 2.3 mmHg and 36.6 +/- 2.2 mmHg (p less than 0.05). The association of inhibition of slow potentials with sphincter relaxation suggests that maintenance of sphincter tone is governed by slow potentials. This proves the diagnostic value of electromyography of the internal sphincter.
Adult↗
The incidence of multiple meningiomas--do solitary meningiomas exist?
Since the advent of computed tomography (CT) the recognition of the occurrence of multiple intracranial meningiomas (MIM) in the same individual has been on the increase. In our material the incidence of MIM at first assessment of CT films was 20%, with distant multiplicity prevailing over the regional one. This incidence will probably change in the course of time as MIM develop not only concurrently but also consecutively. On the other hand our surgical macroscopic incidence of regional multiplicity alone was 49%. The discrepancy between the CT and surgical findings prompted us to reevaluate the CT studies of 100 consecutive patients. This reevaluation demonstrated: 1. in two cases, small meningiomas were overlooked at first assessment; 2. nineteen cases of solitary globoid meningiomas seemed to be the consequence of the coalescence of adjacent smaller masses. Thus, the CT incidence of MIM increased to 40%, with regional multiplicity prevailing over the distant one. The authors think that the aforesaid findings question the very existence of solitary meningiomas as a pathological entity. They would be the end product of a coalescence of multiple adjacent smaller growths. Accordingly, a more aggressive surgical approach is suggested to include the resection of a generous fringe of dura mater around the main tumour. As this is not always possible, or too risky, a comprehensive complement to surgery like radiotherapy could be given a reasonable randomized trial.
Dura Mater↗
Erythrocyte replacement precedes leukocyte replacement during repopulation of W/Wv mice with limiting dilutions of +/+ donor marrow cells.
The severe macrocytic anemia of the stem-cell-deficient W/Wv mouse is alleviated by intravenous injection of normal marrow cells. Donor cells replace the host erythrocytes, but the fate of the more labile blood components, such as granulocytes and platelets, after transplantation into adult mice has not been established. In the present work, the rate of replacement of the various hemopoietic cells in W/Wv transplant recipients was examined by exploiting host-donor differences in cellular markers (hemoglobin and glucose-phosphate isomerase). Limiting dilutions of +/+ parental cells were injected into F1-hybrid W/Wv anemic mice. A dose of 10(5) donor cells was necessary for the implantation of sufficient multipotent stem cells to alleviate the anemia. Erythrocyte parameters were not significantly different from normal values, and donor cells replaced at least 90% of the host erythrocytes by 20 weeks after injection. At this time, only 10% of the nucleated leukocytes and none of the platelets were donor-derived. The percentage of donor lymphocytes, granulocytes, and platelets increased slowly thereafter but did not completely replace the host elements by 41 weeks. The maintenance of host leukocytes during rapid donor-erythrocyte replacement indicates cell-specific amplification of committed progenitors.
Anemia, Macrocytic↗
Functional versus structural changes of forearm vascular resistance in hypertension.
Structural changes in resistance vessels have been considered an important factor in triggering and maintaining chronic hypertension in humans and in experimental animals. To determine whether the increased forearm vascular resistance observed following vasodilator maneuvers in hypertensive patients is predominantly due to structural or to functional changes, we examined the influence of different vasodilator stimuli on forearm blood flow and blood pressure in 22 male patients with established essential hypertension and in 22 age-matched normotensive men (age range, 28-52 years). Blood pressure was measured directly, and blood flow was measured by venous occlusion plethysmography. The maneuvers applied were 1) arterial occlusion combined with handgrip exercise and local heating, 2) intra-arterial infusion of the calcium entry blocker nifedipine, 3) intra-arterial infusion of the nonspecific vasodilator sodium nitroprusside, 4) arterial occlusion initiated after intra-arterial infusion of nifedipine. Vascular resistance during vasodilation induced by arterial occlusion or infusion of nifedipine or sodium nitroprusside remained significantly higher in the hypertensive than in the normotensive subjects. However, the maximal vasodilation achieved by the combination of arterial occlusion and nifedipine resulted in a similar resistance in both groups (1.6 +/- 0.2 in the hypertensive vs 1.4 +/- 0.2 mm Hg/ml/min/100 ml tissue in the normotensive subjects. These data suggest that there is an important functional component of the elevated resistance in patients with essential hypertension.
Adult↗
Inducible Ig heavy chain switching in an IgM+ Ly-1 B cell line. Evidence for a state of switch commitment.
We have analyzed the pattern of immunoglobulin (Ig) heavy chain isotype secretion in AJ9, a cloned, IgM+ murine B lymphocyte cell line. Upon induction by a variety of lymphokines and polyclonal B-cell activators, AJ9 cells express multiple subclasses of IgG and IgA in addition to IgM. In certain cases, mature isotype is restricted--e.g., IL-5 predominantly elicits production of IgG2 and IgA, a restriction also observed in short-term lymphocyte cultures. In other cases (e.g., anti-IgM plus 8-mercaptoguanosine, a polyclonal B-cell activator) production of mature isotypes is unrestricted. Under optimal conditions, only a low abundance of secreted Ig and low frequency of secreting cells (less than 0.5%) were detected. A serial cloning assay was devised to define the pattern of isotype switching in induced cells and their progeny. We expected to observe a progressive limitation of progeny to expression of single mature isotypes. Surprisingly, nearly all subclones of the induced cells were found to produce a range of mature isotypes. Sequential cloning in basal medium revealed that this induced phenotype persisted for more than a month (greater than 40 generations). Throughout this period, the abundance of mature isotype production remained low, and membrane Ig was exclusively of the IgM isotype. We interpret this induced response to reflect an intermediate state of B-cell differentiation, in which cells become committed to the switching process, but are not adequately stimulated to efficiently complete the process required for expression of mature isotypes. These findings are discussed in regard to the control of the switching process, and their possible relevance to the memory state of B cells.
Animals↗
[Anti-elastolytic inhibitory capacity and IgA deficiency--contribution to the etiopathogenesis of COPD].
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Agammaglobulinemia↗
Determination of sotalol in human body fluids for pharmacokinetic and toxicokinetic studies using high-performance liquid chromatography.
A sensitive, reliable and discriminating assay method is reported for the determination of sotalol (4-(1-hydroxy-2-isopropylaminoethyl)methanesulfonanilide) in human plasma and urine. The assay procedure has been successfully used during pharmacokinetic studies in healthy volunteers and patients as well as during toxicokinetic analysis. For sample preparation the internal standard atenolol was added to the specimen which was then extracted with n-pentanol-chloroform (1/3) at pH 9.0 followed by re-extraction into 0.05 mol/l sulfuric acid. Chromatography with fluorimetric detection was performed on Hypersil ODS 5 micron including the addition of heptanesulfonic acid and sodium dodecyl sulfate to the mobile phase of acetonitrile-water-acetic acid (20/79/1). Calibration was linear over the ranges of 0.1 to 5.0 micrograms/ml and 0.2 to 100 micrograms/ml for plasma and urine, respectively. Over these ranges coefficients of variation were below 10%. Recovery was between 82 and 98% from plasma and between 92 and 99% from urine.
Biological Availability↗
[IGA concentration in serum, sputum and bronchoalveolar lavage in chronic bronchitis].
IgA concentrations in serum, sputum and bronchoalveolar lavage were determined in 11 patients with chronic obstructive lung disease exacerbated by infection and in 22 with similar disease during an infection-free period. Patients with infection had a higher serum-IgA concentration than those without. But there was no difference in sputum-IgA concentration between the two groups. Both for sputum and broncho-alveolar lavage there was a positive correlation between anti-elastolytic inhibition capacity and IgA concentration. In vitro it has been demonstrated that IgA concentration measured immunologically decreases with increasing elastase concentration, in line with increasing free elastolytic activity. Local IgA deficiency in patients with infection apparently results from proteolytic splitting of the immunoglobulin.
Adult↗
Elevated myc expression and c-myc amplification in spontaneously occurring B lymphoid cell lines.
Recently, a minor subpopulation of murine B lymphocytes, Ly-1+ B cells, has been distinguished by its unique ontogeny, tissue distribution, and prominence in certain autoimmune and neoplastic B cell diseases. We have previously described a simple murine spleen culture system that results in the spontaneous and exclusive outgrowth of long-term Ly-1+ B cell lines (B Ly-1 cells). Here, we report that the immortal growth property of B Ly-1 cells correlates with a 10-45-fold elevation of steady-state myc RNA and 2-10-fold amplification of the c-myc locus. While c-myc amplification has been observed in malignant cell lines derived from several tissues of origin, its occurrence in lymphoid cells has not been previously reported. The consistent c-myc amplification in B Ly-1 cells may reflect a unique state of this locus in the Ly-1+ B lymphocyte lineage, and contribute to the spontaneous immortalization of this B cell population in vitro, and its apparent predilection for malignant transformation in vivo.
Animals↗
Idiotype-specific Ly-1 B cell-mediated helper activity: hybridomas that produce anti-idiotype antibody and nonimmunoglobulin lymphokine(s)1.
Previous work has shown that the expression of a predominant family of idiotypic determinants (NPb) in the in vitro response to the 4-hydroxy-3-nitrophenyl acetyl (NP) hapten is dependent on helper activity provided by Ly-1- and Ig-bearing B cells called BH. The ability of these BH cells to perform this idiotype-specific, genetically controlled helper function is related to the NPb idiotype specificity of their cell surface receptors. However, the means by which BH cells communicate with and stimulate NPb idiotypic B cell subsets is unknown. In this paper, an Ly-1- and immunoglobulin-bearing B helper cell hybridoma is described. Supernatants from the hybridoma or its subclones were shown to specifically help the response of NPb idiotypic PFC to NP-Ficoll when added to responder cell cultures depleted of Thy-1 and Ly-1 regulatory cell populations. Under these experimental conditions hybridoma supernatants functioned in much the same fashion as populations of Ly-1- and Ig-bearing BH helper populations described previously. NPb idiotype-specific helper activity was mediated by two separable activities elaborated by the hybridoma, an anti-NPb idiotype antibody and a non-Ig (lymphokine) activity. It was shown that both the Ig and the lymphokine components were required for helper activity. Kinetics experiments showed that the anti-idiotype antibody must be added early in the response to NP-Ficoll, whereas the lymphokine fraction could be added at least as late as day 3 of a 4-day culture in order to observe NPb idiotype-specific help. The data suggest that Ly-1 B cell hybridomas may affect the responsiveness of B cell subsets initially by interaction of anti-idiotype antibody with NPb idiotypic B cell surface receptors, followed by growth or maturation signals mediated by non-Ig lymphokine(s). The possibility that the helper activity of these Ly-1 B cell hybridomas represents the combined effects of an idiotype-specific network system and nonspecific growth or maturation factor activity in direct B cell-B cell interactions is discussed.
Animals↗