Bullous diseases: unapproved treatments or indications.
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Biomedical subjects
Publications and source records attributed to R Wolf.
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The immune system of higher organisms is composed largely of two distinct cell types, B lymphocytes and T lymphocytes, each of which is independently capable of recognizing an enormous number of distinct entities through their antigen receptors; surface immunoglobulin in the case of the former, and the T-cell receptor (TCR) in the case of the latter. In both cell types, the genes encoding the antigen receptors consist of multiple gene segments which recombine during maturation to produce many possible peptides. One striking difference between B- and T-cell recognition that has not yet been resolved by the structural data is the fact that T cells generally require a major histocompatibility determinant together with an antigen whereas, in most cases, antibodies recognize antigen alone. Recently, we and others have found that a series of TCR V beta gene sequences show conservation of many of the same residues that are conserved between heavy- and light-chain immunoglobulin V regions, and these V beta sequences are predicted to have an immunoglobulin-like secondary structure. To extend these studies, we have isolated and sequenced eight additional alpha-chain complementary cDNA clones and compared them with published sequences. Analyses of these sequences, reported here, indicate that V alpha regions have many of the characteristics of V beta gene segments but differ in that they almost always occur as cross-hybridizing gene families. We conclude that there may be very different selective pressures operating on V alpha and V beta sequences and that the V alpha repertoire may be considerably larger than that of V beta.
UNLABELLED: At the age of 5 years, a boy with known multicystic dysplastic kidney disease showed signs of arterial hypertension with progress to fatal hypertensive encephalopathy. Arterial hypertension was refractory to antihypertensive therapy and the child lost consciousness. Computed tomography of the brain revealed multiple cerebral infarctions. Doppler ultrasound showed an elevation of blood flow in the main artery of the functioning kidney consistent with stenosis as a cause of hypertension. CONCLUSION: Arterial hypertension is a known complication of kidney disease. Multicystic dysplastic kidney and renal artery stenosis is a potentially fatal association. Careful evaluation and monitoring, with special emphasis on blood pressure, should be performed in children with multicystic dysplastic kidney disease.
Basic fibroblast growth factor (bFGF) is a pleiotropic growth factor which has a high capacity for stimulating normal melanocyte proliferation and suppressing melanogenesis. The close and complicated relationship between bFGF, melanocyte proliferation and melanogenesis raises the theoretical possibility that bFGF may also be involved in the pathomechanism leading to vitiligo. The aim of this study was to compare the serum and suction blister fluid bFGF levels of vitiligo patients (9 females, 11 males) with those of healthy controls (3 females, 8 males). Vitiliginous skin-blister fluid bFGF levels and serum levels were significantly higher in vitiligo patients compared with healthy normal controls. Our data indicate that bFGF might be involved in the pathogenetic chain of events leading to vitiligo. Further studies are needed to define the exact role of bFGF and various other melanocytic mitogens in this disease.
The biotransformation of the 131I-labeled cholegraphic media ioglycamic acid, iodoxamic acid and iotroxic acid in man is investigated. Plasma, urine and fistular bile were analyzed for unchanged and metabolized constituents of the administered substances using thin layer chromatography. No metabolites were found in plasma, but up to two were found in urine in addition to unchanged contrast media (a total of 50% of the total elimination in 24 hr. urine). A metabolite was only found in the fistular bile after the injection of iotroxic acid.
A 38-year-old woman developed focal nodular hyperplasia of the liver after she had received a 4-month treatment with intraconazole 200 mg/d for a fungal infection of her fingernails. Because the patient underwent yearly liver ultrasound examinations because of the removal of a breast carcinoma, when the tumor was discovered incidentally, it was clear that it had developed within the past year after she had begun receiving intraconazole. Although various chemical agents and drugs have been considered as possible etiologic factors in the development of focal nodular hyperplasia of the liver, cases occurring after intraconazole therapy have not been reported before. Apart from the theoretical considerations with regard to the pathogenesis of nodular hyperplasia of the liver, this case could gain practical importance, as it shows a new adverse effect of a drug that has been used in more than 34 million patients over the past 10 years. Furthermore, this case should draw attention to the possibility of drug-induced benign hepatic tumors, as they may mimic malignant and metastatic disorders, which might be especially alarming in patients undergoing routine examinations after removal of malignant tumors, such as our patient.
Since the majority of persons with alcohol, drug abuse, and/or mental disorders (19%) of Americans during any 6-month period are seen exclusively within the general health sector, it is imperative to know the quality and quantity of mental health training for primary care residents. In this study, the five program training model types previously described--Consultation, Liaison, Bridge, Hybrid, Autonomous--are validated by a random sampling technique using a structured instrument to test eight hypotheses developed before data collection to preclude post hoc interpretations. Of 250 programs, 147 responded (60%): 67 Family Practice, 42 Primary Internal Medicine, and 38 Internal Medicine. Since all eight hypotheses were supported by the data, the construct validity of the program model types is significantly substantiated. Multiple discriminant analysis revealed that the relationships between twelve training program characteristics and the five program model types were such that the former could explain 57% of the variance in the latter and correctly classify 89% of the programs.
Drosophila flies can be trained in the flight simulator to operantly avoid heat by choosing certain orientations relative to landmarks. Flies primarily store pattern orientations associated with the absence of heat. They readily escape from heat-associated orientations under the direct influence of the reinforcer but not in the subsequent memory tests. The flies tend to keep the largest possible distance from the "hot" or potentially "hot" regions, that is, they head toward the center of the "cold" sector. The results are discussed in the light of the retinotopic matching model explaining visual memory in flies by the superposition of a retinotopically stored template with the actual retinal image. Window experiments confining visual feedback to two 90 degrees sectors indicate that the memory template covers most of the visible space.
Orientation preferences for visual patterns can be conditioned in tethered flies (Drosophila melanogaster) at the flight simulator. In a reversal conditioning procedure using heat as reinforcement, flies can be trained to successively prefer different flight orientations with respect to the patterns. As in many learning paradigms, conditioned responses are highly variable. Although during training most flies reliably avoid the heat and the corresponding flight orientations, in subsequent learning tests without heat some show no consistent preference for the permissive orientations. We have started to investigate the interindividual differences in learning performance and describe here three significant variables: the age of the animals, their experience in the flight simulator prior to the experiment, and the composition of the fly food. Flies learn more reliably at 3-4 days than at 1-2 days of age but learning indices do not increase further in even older flies. Learning is improved if flies are allowed to become familiar with the flight simulator before the start of the conditioning procedure. Most important, poor nutrition causes complete amnesia within three or four generations. The reverse shift from poor to nutritious food restores learning ability with an even longer delay.
Organisms navigating by path integration need to continuously measure their forward movement and their angular orientation with respect to an external reference. How they do it is little understood. Tethered flies at the flight simulator "navigate" in an artificial visual landscape without forward movement. They can return to a previously held orientation if the panorama provides a singularity (landmark) as reference. Surprisingly, in a regularly striped drum without singularities, they can use a temporal cue instead. In this experiment the arena is illuminated with only one color that is either green or blue. The arena is virtually divided into four quadrants. Whenever a quadrant boundary moves past an arbitrary point, the color of the arena light changes. When a fly is heated with one color it acquires a preference for the other one. Subsequently, it avoids the borders toward the potentially 'hot' quadrants even without touching them. The only way to achieve this is by turn integration, that is, by adding and subtracting all the turns it performs once it crosses the border. The color switch defining the border crossing resets the turn integrator, using the orientation of the arena at this moment as reference. In contrast, landmarks or, if it were available, the skylight compass enable the fly to establish by pattern learning any orientation as a reference. If the reference orientation coincides with the desired orientation, that is, if the animal stores the pattern while being oriented toward the goal, it can maintain its orientation without recourse to turn integration (which may be error prone).
The flexibility of behavior is so rich, and its components are so exquisitely interwoven, that one may be well advised to turn to an isolated behavioral module for study. Gill withdrawal in Aplysia, the proboscis extension reflex in the honeybee, and lid closure in mammals are such examples. We have chosen yawing, a single component of flight orientation in Drosophila melanogaster, for this approach. A specialty of this preparation is that the behavioral output can be reduced beyond the single module by one further step. It can be studied in tethered animals in which all turns are blocked while the differentially beating wings still provide the momentum. These intended yaw turns are measured by a torque meter to which the fly is hooked. The fly is held horizontally as if cruising at high speed. The head is glued to the thorax. It can bend its abdomen, extend its proboscis, and move its legs but cannot shift its direction of gaze or its orientation in space. Evidently, a fly hardly ever encounters this bizarre situation in the wild. We describe here the flexibility in this single behavioral variable. It provides insights into the relation between classical and operant conditioning, the processing of and interactions between the conditioned visual stimuli, early visual memory, visual pattern recognition, selective attention, and several other experience-dependent properties of visual orientation behavior. We start with a brief summary of visual flight control at the torque meter.
The influence of bradykinin, a component of the kallikrein-kinin system, on the motility of ram spermatozoa was examined in vitro (photometric motility evaluation, penetration test in cervical mucus of sheep, estimation of the percentage of forward-moving spermatozoa in the thermal resistance test). Whereas the motility was found to be influenced by bradykinin the acrosomal status remained undisturbed by it. With fresh as well as with frozen semen, the drug mainly increased the motility of samples with a low initial motility. With frozen semen, the penetration test revealed greater motility rises at 22 degrees C than at 38 degrees C. The importance of the results in relation to the angiotensin-converting enzyme (kininase) as well as the motility evaluation capabilities of the methods used are discussed. There was, however, no positive drug effect after adding the drug in the course of cryopreservation prior to freezing semen in straws although bradykinin solutions frozen in liquid nitrogen maintained their effectiveness.
In vivo effects of carbamazepine (CBZ) on the neuroendocrine preopticopituitary feedback system were studied by local application of CBZ through a push-pull cannula into the preoptic area and measurement of local effects on gamma-aminobutyric acid (GABA) and distant effects on a subsequent biologic response: luteinizing hormone (LH). Perfusion with 8 and 12 micrograms CBZ/ml cerebrospinal fluid caused a reduction in preoptic GABA release and concomitant suppression of plasma LH levels. These results suggest a GABA component to the mechanism(s) of action of CBZ: (a) CBZ reduces extracellular available GABA concentration, and (b) owing to the known inhibitory role of preoptic GABA in pituitary LH secretion, an increase of postsynaptic GABAergic transmission by CBZ itself could be inferred.
To study further the previously demonstrated suppressive in vivo effect of sodium valproate (VPA) on gamma-aminobutyric acid (GABA) release in the preoptic area, we examined GABA neurotransmission in substantia nigra (SN), using the push-pull cannula technique in freely moving ovariectomized rats. To clarify whether the area in the substantia nigra that is actually perfused is pars reticulata, known to receive rich GABAergic input from striatum, we used the retrograde fluorescence tracer fast blue (FB) after each perfusion experiment, applying the tracer through the push-pull cannula. Nigral perfusion with VPA caused significant suppression of local GABA release. This effect was more marked in a subgroup of animals showing retrograde labeled cell bodies in striatum, i.e., animals with a tracer application site and therefore also a perfusion site precisely in pars reticulata. Our data suggest that VPA inhibits GABA release in rat SN as it does in the preoptic area, which may be in agreement with our hypothesis of enhanced GABAergic neurotransmission by VPA, causing suppression of presynaptic GABA release through negative feedback actions on the GABA autoreceptor complex. Furthermore, the combination of push-pull cannula technique and retrograde fluorescence tracer application appears to be an important tool to prove afferent connections of the area actually perfused in neuronal networks.
Lipid model systems consisting of the major components of the stratum corneum intercellular lipid matrix were studied to investigate the ultraviolet-radiation-mediated damage of these biomolecules. Pure lipids and liposomes were irradiated using a lamp emitting a solar radiation spectrum. The influences of the irradiation and the effects of added iron ions were studied by electrospray ionization mass spectrometry (MS) with an ion trap analyser. Exact mass measurements were carried out using a time-of-flight mass spectrometer. Only linolenic acid and cholesterol were found to be subject to oxidative changes caused by UV irradiation whereas the other lipids examined (dipalmitoylphosphatidylcholine, ceramide III and cholesterol sulphate) were stable to oxidative stress. Several lipid adducts were observed upon analysis of the liposomes. The composition of these adducts was identified by MS/MS experiments.
The usage of a 6 V lithium manganese dioxide battery results in a significant reduction of capacitor loading time within implantable defibrillators/cardioverters. In order to provide ERI indication a new cathode formulation has been developed. The battery shows no voltage delays, a low self-discharge and fulfilled all requirements to an energy source for an implantable device.