Substitution studies and the nature of superconductivity in UPt3.
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Biomedical subjects
Publications and source records attributed to K Bakker.
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Chimeric M-T412 (cM-T412), an anti-CD4 antibody, was tolerated in chimpanzees at a dosage of 5 mg/kg per day for up to 7 consecutive days, or 5 mg/kg per dose, twice weekly for 4 weeks. All cM-T412-treated chimpanzees showed a prolonged CD4-cell depression. Weak chimpanzee antibody responses to chimeric M-T412 were observed. One of the chimpanzees on the biweekly dosage regimen exhibited a hypersensitivity reaction immediately after receiving its seventh dose. Following supportive treatment, the animal recovered and remained asymptomatic during the non-treatment observation period. The hypersensitivity reaction was not an unexpected response considering the animal received repeated intermittent i.v. administration of a foreign protein. This animal also showed a chimpanzee antibody response to chimeric M-T412 after the seventh dose. Chimeric M-T412 also induced an anti-cM-T412 response in some of the other animals. The level of this response was lower than the anti-mouse responses observed in animals treated with murine anti-CD4. Moreover, the anti-cM-T412 response was mainly directed to idiotypic determinants. The decrease in CD4+ cells observed for all chimeric M-T412-treated chimpanzees is an expected effect of the anti-CD4 antibody. The duration of this CD4+ cell decrease is, however, much longer than observed for other CD4-specific MoAbs described. No selective loss of either memory or naive CD4+ cells was observed after either the single, 7-day or twice-weekly treatments. The CD4+ cell depression was reversible, although individual variation in time to recovery was observed. Therefore, cM-T412 could be a good candidate for clinical use in autoimmune conditions.
Two patients with non-insulin-dependent diabetes mellitus and previously undiagnosed peripheral neuropathy consulted separate practitioners in alternative medicine with symptoms of painful cold feet. They both received the traditional Chinese therapy of moxibustion and subsequently developed painless ulceration at the sites of treatment on the feet and legs. These cases re-emphasize the dangers of trauma to the neuropathic limb in patients with diabetes.
Several studies have suggested that ACE-inhibition may be effective in postponing the onset of nephropathy in insulin-dependent diabetic subjects. In contrast, other drugs might have opposing effects. To study the long term effects of either captopril or nifedipine in normotensive, microalbuminuric patients with insulin-dependent diabetes mellitus, eighteen subjects received either placebo (n = 5, P), 20 mg nifedipine daily (n = 7, N) or 50 mg captopril daily (n = 6, C) for one year. Baseline clinical and laboratory variables were comparable in the three groups. Glomerular filtration rate (GFR), effective renal plasma flow (ERPF) and blood pressure did not differ between groups before and after one years medication. UAER did not change in the captopril and the placebo group (C: -12.6% (-58.1 to 51.8%)' P: -17.3 (-55.9 to 99.3%), medians and ranges. In contrast, in the patients that received nifedipine, UAER rose by 43.1% (-8.5 to 261.8%), (p < 0.05 Baseline vs one year, and one year nifedipine vs captopril and placebo). We therefore conclude, that long-term use of nifedipine increases UAER in normotensive microalbuminuric insulin-dependent subjects, in contrast to captopril or placebo. Whether this enhancement of microalbuminuria exerts an adverse effect on renal function in the long-term is yet unknown, but caution seems warranted.
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Two autoimmune disease models were studied in rhesus monkeys: type II collagen-induced arthritis (CIA) and experimental allergic encephalomyelitis (EAE). Unrelated outbred animals were used in these studies. In both models disease resistant and susceptible individuals could be identified. Susceptibility correlated with in vitro cellular responsiveness to antigen in the CIA model. In both models resistant as well as susceptible individuals developed a humoral response to the inducing antigen. However, there is an indication that IgM antibodies play a crucial role in the induction of CIA. No clear association between major histocompatibility complex (MHC) type and disease incidence was found although a higher frequency of a certain DR type was observed in EAE susceptible monkeys. It is likely that both the antigen binding capacity of the MHC class II molecules and the T-cell repertoire play an important role in determining whether disease will develop or not.
Speech-related reaction time measures (laryngeal premotor and adjustment time for /a/, labial initiation and physiological voice onset time for /pa/) and fluency-related measures (number of stutterings, number of normal disfluencies, and time needed to complete an oral reading) of 24 stutterers and a like number of nonstutterers were assessed to determine their diagnostic discriminative power. Discriminant analysis showed that stutterers were most effectively differentiated from normally fluent speakers by the total number of stutterings and normal disfluencies during oral reading and by the duration of laryngeal adjustments prior to cued phonation. Factor analysis revealed that the fluency failure and reaction time measures clustered independently for both stutterers and nonstutterers. These findings suggest that both fluency failures and the duration of laryngeal adjustment time are useful diagnostic measures for discriminating stutterers from those who are normally fluent.
The laryngeal premotor, adjustment, and reaction times of 24 stutterers and 24 nonstutterers were assessed by means of a group (2) by stimulus modality (3) by stimulus order (6) factorial investigation. The laryngeal measures were determined from print outs made from electroglottographic recordings taken during the production of [a] that was cued by a visual, auditory, or somato-sensory stimulus. The results revealed that the laryngeal reaction times of stutterers were significantly longer than those of the nonstutterers. Moreover, the reaction times were significantly longer both during the laryngeal premotor and adjustment time periods. The observed between-group difference for each of these laryngeal measures was independent of the stimulus that was employed.
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Buspirone is a novel anxiolytic whose pharmacological profile differs from that of the benzodiazepines and includes dopaminergic agonist effects. Because of these properties, buspirone's usefulness in the management of idiopathic Parkinson's disease was evaluated in a controlled study of 16 outpatients with stage I-IV disease. At doses of 10 to 60 mg/day, no significant group or individual effects could be discerned on standardized disability, dyskinesia, anxiety, or depression scales. At high dose levels (100 mg/day) however, there was a significant worsening of disability ratings and a decrease in dyskinesia scores; anxiety ratings were also significantly increased. The results indicate that buspirone is well tolerated by parkinsonian patients at conventional antianxiety doses of 10 to 40 mg. Clinical effects of high dose treatment, on the other hand, resemble those associated with a reduction in central dopamine mediated synaptic function. Since buspirone reportedly produces dose-dependent stimulation of norepinephrine containing neurons in the locus ceruleus and behavioral symptoms of such activation were observed, these clinical observations support the concept that central noradrenergic stimulation can adversely affect parkinsonian symptoms.
In view of evidence linking cholecystokinin-containing neurons with both dopamine system function and Parkinson's disease pathophysiology, the therapeutic effects of the cholecystokinin analog, caerulein, were evaluated in 10 parkinsonian patients stabilized on L-Dopa therapy. Despite substantially elevated plasma caerulein levels immediately following intramuscular injection of this peptide, no consistent change in neurologic status could be discerned. These negative results may be due to the relatively small amounts of caerulein entering the CNS at dose levels that do not induce gastrointestinal toxicity.
During the silent reading of a 320-word passage, the eye movements of 22 grade school stutterers and 22 nonstutterers were recorded by means of a computer-controlled eye-marker. The recordings were made as a means of determining if the eye movements of the two groups differed and if the differences suggested that the young stutterers showed evidence of word-specific expectancy. Frame-by-frame analysis of the recordings revealed that the stuttering children displayed significantly more eye fixations and eye regressions than the nonstuttering children. The correlations among the different types of eye measures also varied between the subject groups. The differences observed were present despite the fact that the reading level of the two groups was age appropriate and the subjects sampled did not differ significantly in either reading errors or comprehension. These findings are like those previously found when stuttering and nonstuttering adults were similarly tested. They imply that expectancy is not the response province of older stutterers.
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Analysis of the geometry of the beating heart may yield important information about its condition and function, and may reveal physiologically and clinically relevant information about the influence of regional malfunctioning on the integral heart performance. In this study, a method has been developed which will ultimately allow the determination of the three-dimensional geometry of an isolated working dog-heart throughout the cardiac cycle. The technique will be called 'ultrasound velocity tomography'. Ultrasound velocity tomograms are reconstructions of the spatial distribution of the ultrasound velocity in cross-sections of the object under study. This velocity is to a certain extent characteristic for a tissue, so that various tissues and structures can be identified in a tomogram. The velocities are mathematically reconstructed from thousands of measured times-of-flight of ultrasound pulses which have travelled along different path-ways through the object. By detecting the blood-heart muscle transitions in a tomogram and by combining tomograms from different cross-sections of the heart, a three-dimensional heart-geometry may be obtained. Preliminary results on a formalin-fixed heart are shown and discussed.
In three patients with Bartter's syndrome, indomethacin administration resulted in the disappearance of the hypokalemic alkalosis and in a normalization of the elevated plasma renin activity. Changes in calcium and phosphate metabolism during indomethacin medication seemed to indicate an increase in reabsorption activity of the renal proximal tubulus. A kidney biopsy performed in one of the patients showed, besides hyperplasia of juxtaglomerular cells, hyperplasia of interstitial medullary cells which are presumed to produce prostaglandins. As indomethacin is a well-known inhibitor of prostaglandin synthesis, the observations suggest that an overproduction of renal prostaglandins could well be of pathogenetic significance in Bartter's syndrome.
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