Biomedical subjects
Publications and source records attributed to P Mayer.
We have developed a new and simplified injection technique based on a mixture of latex and lead oxide. This injection technique is unique in its possession of both color and radio-opacity. We have developed and refined this methodology in rats, and have demonstrated it to possess superior qualities of injectability. Depiction of small vessels is highly detailed both radiographically and grossly.
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BACKGROUND: Recombinant birch pollen allergens Bet v 1 and Bet v 2 (birch profilin) have been characterized in vitro previously. OBJECTIVE: To establish a close-to-man model of type I allergy, recombinant birch pollen allergens were injected into rhesus monkeys. METHODS: The allergens were expressed in Escherichia coli, purified to homogeneity and injected into rhesus monkeys with aluminium hydroxide as adjuvans. The development of type I allergy was monitored by measurement of specific IgE, in vitro histamine release tests, cellular proliferation assays, skin testing, and bronchial provocation tests. RESULTS: Immunized rhesus monkeys displayed symptoms of type I allergy comparable to those of allergic patients, and cross-reactivity of IgE antibodies with Bet v 1 and Bet v 2 homologous allergens was observed. Systemic application of corticosteroids during secondary immunizations suppressed specific antibody responses. CONCLUSION: Recombinant birch pollen allergens (Bet v 1 and Bet v 2) were effective to establish a close-to-man model of natural type I allergy in rhesus monkeys, allowing study of specific IgE regulation in vivo.
BACKGROUND: Serologic measurements with recombinant birch pollen allergens, rBet v 1 and rBet v 2 (birch profilin), have shown that more than 95% of patients allergic to tree pollen mount high levels of IgE against rBet v 1, whereas only approximately 10% of the patients display rather low levels of IgE against rBet v 2. OBJECTIVE: In this study an attempt was made to determine whether the different allergenicity of the major birch pollen allergen, rBet v 1, and a minor birch pollen allergen, rBet v 2, might be related to a different immunogenicity of the proteins as evaluated in experimental animal systems (mice and rhesus monkeys). METHODS: Purified recombinant allergens were injected into mice and rhesus monkeys with aluminum hydroxide as adjuvant for elicitation of specific IgE responses. Antibody responses to the allergens were detected by immunoblotting, and time courses of immune responses were measured by ELISA. RESULTS: In both animal models more than the 10-fold dose of rBet v 2 was required to induce IgE antibodies, and even then, the amount of specific IgE antibodies elicited with rBet v 1 was substantially higher than that induced by rBet v 2. It was noted that rBet v 2 formed stable polymers through disulfide bonds. CONCLUSION: In two different animal models (mice and rhesus monkeys) the major birch pollen allergen, rBet v 1, induced substantially higher levels of IgE than rBet v 2. A reduced allergenicity of Bet v 2 caused by polymer formation would be in agreement with previous studies indicating reduced allergenicity of proteins on chemical polymerization.
Eighty-five consecutively seen HIV-positive persons with oral candidiasis were evaluated for clinical characteristics, staging of HIV disease, quantitation of candidal colony formation, and response to systemic antifungal treatment with Nizoral (ketoconazole). Fifty-five had CD4 counts less than 200. There was an inconsistent association between clinical signs, patient symptoms, CD4 counts, and candidal colony-forming units. However, there was a trend toward higher colony-forming unit counts (> 500) in patients with lower CD4 cells (< 200). Sixty-five patients had a complete clinical response to the ketoconazole treatment (200 mg daily for 7 days), even though 81% of posttreatment cultures remained positive. Nonsmokers were more likely to respond to antifungal treatment when compared with smokers, and there was a slight tendency for complete responses when colony-forming unit counts were low. The most common lesion presentation was a combination of the white (pseudomembranous) and red (erythematous) forms. Forty-nine percent had complaints of pain. The variable responses indicated the importance of flexible dose-time and drug considerations in antifungal management. Candida albicans was the predominant species.
The actions of exogenous and endogenous opioids are mediated by at least three different opioid receptors, called mu, kappa, and delta. Recently, we have detected a new variant of the rat mu-opioid receptor, which we termed rMOR1B and which differs from rMOR1 (now also called rMOR1A) in the amino acid sequence at the C-terminus. Both isoforms were proposed to be splicing variants of the same gene. To elucidate the molecular mechanism leading to the formation of the new variant, the exon/intron structure of the rat mu-opioid receptor gene in the respective area has been determined by analyzing a genomic P1 phage clone. In addition, we have investigated the putative promoter region of this gene. The present study revealed that rMOR1B is generated by an alternative splicing event whereby a previously unknown exon will be placed behind exon 3 to form rMOR1B mRNA, which is separated from the latter by an intron. Therefore, this new exon has to be called exon 4, whereas the former exon 4, which encodes the C-terminus of MOR1A, now becomes exon 5. Examination of the putative rat promoter region revealed a high degree of nucleotide sequence homology to the mouse gene. Using an RNase protection approach, one single transcription initiation site could be located at 230 bp upstream of the translation start. This is similar to the situation in the mouse, where four major transcription start sites were reported to lie close together around 270 bp upstream of the protein coding region.
The spectrum of respiratory sleep disorders has been extended in the last years to include conditions that are less well defined than severe obstructive sleep apnea (OSA). Moderate OSA, snoring, and upper airway resistance syndrome (UARS) represent three conditions in which there are still unresolved pathophysiological, epidemiological, and clinical questions. Therefore, the therapeutic approach remains unclear. We have tried to define these entities and to review the respective indications and efficacy of pharmacological treatment, weight loss, sleep posture, oral appliances, upper airway surgery, and finally, continuous positive airway pressure (CPAP). From these data, we also aim to define strategies of treatment for moderate OSA, snoring, and UARS. However, these conditions are likely to be particularly appropriate for randomized trials comparing different modalities of treatment that may be the only way to validate these treatment strategies.
Surgery is widely considered to be the first-line therapy for "simple" snoring and moderate sleep apnea syndrome. Surgical treatment of severe obstructive sleep apnea (OSA) is currently generally considered to be second-line therapy after continuous positive airway pressure (CPAP) treatment. Many patients, however, find difficulty in complying with the continued long-term demands of CPAP treatment and seek a more definitive one-off solution to their sleep-related problem. Surgical therapy has been found useful for snoring, at least on subjective grounds; this has incited patient demand and led surgeons to expand its use for upper airway resistance syndrome (UARS) and possibly OSA. In this paper the surgical procedures of uvulopalatopharyngoplasty (UPPP), nasal surgery, and maxillofacial surgery are discussed and analyzed as they relate to the resolution of snoring, UARS, and OSA. There are many methodological problems in the published literature that make this analysis difficult. We feel that surgical therapy should be comparable to CPAP therapy, fulfilling the same analytical criteria in regard to measurement of severity and improvement of the disorder, as well as an equally sustained effect. Operative risk and side effects need to be clearly stated. Guidelines for future data collection and clinical trials of surgical procedures are proposed, and we recommend randomized prospective multicenter protocols and a registry of patients undergoing surgery for OSA so that long-term follow-up can be achieved.
Numbers of interleukin-12 (IL-12) producing cells were quantitated in the peripheral blood of healthy donors and tuberculosis patients by the ELISPOT assay. We observed that (i) stimulation with mycobacteria increases numbers of IL-12 producers from healthy donors and (ii) tuberculosis patients have larger numbers of IL-12 producers than healthy donors. Our data emphasize the importance of Il-12 in immunity to tuberculosis.
Anatomical pharyngeal and craniofacial abnormalities have been reported using upper airway imaging in snorers with or without obstructive sleep apnoea (OSA). However, the influences of the age and weight of the patient on these abnormalities remain to be established. The aim of this study was, therefore, to evaluate in a large population of snorers with or without OSA, the relationship between body mass index (BMI), age and upper airway morphology. One hundred and forty patients were referred for assessment of a possible sleep-related breathing disorder and had complete polysomnography, cephalometry and upper airway computed tomography. For the whole population, OSA patients had more upper airway abnormalities than snorers. When subdivided for BMI and age, however, only lean or younger OSA patients were significantly different from snorers as regards their upper airway anatomy. The shape of the oropharynx and hypopharynx changed significantly with BMI both in OSA patients and snorers, being more spherical in the highest BMI group due mainly to a decrease in the transverse axis. On the other hand, older patients (> 63 yrs), whether snorers or apnoeics, had larger upper airways at all pharyngeal levels than the youngest group of patients (< 52 yrs). For the total group of patients, upper airway variables explained 26% of the variance in apnoea/hypopnoea index (AHI), whereas in lean (BMI < 27 kg.m-2) or youngest (age < 52 yrs) subjects upper airway variables explained, respectively 69 and 55% of the variance in AHI. In conclusion, in lean or young subjects, upper airway abnormalities explain a major part of the variance in apnoea/hypopnoea index and are likely to play an important physiopathogenic role. This study also suggests that the shape of the pharyngeal lumen in awake subjects is more dependent on body mass index than on the presence of obstructive sleep apnoea. Further investigation looking at upper airway imaging for surgical selection in obstructive sleep apnoea should focus on lean and young patients.
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The rat mu opioid receptor gene promoter was cloned and characterized. It has a few features in common with the mouse gene, e.g. the lack of a classical TATA box and the fact that several transcriptional start sites are used. The overall homology between the two species is greater than 85%. Functional analysis of the promoter was performed using transient expression of rat mu opioid receptor-reporter gene constructs in the mu opioid receptor expressing cell line SH SY5Y and in non mu opioid receptor expressing cell lines. A promoter region was defined which confers both high basal and TPA and forskolin stimulated reporter gene expression in SH SY5Y cells.
Because the local electrical resistance is inversely proportional to the local cross-section of a capillary, the intensity of the electric field varies along the migration path if the inner diameter of the capillary is not constant. Therefore, fluctuations of the lateral dimensions of a capillary can directly affect the net elution time as well as the peak width, and, hence the final resolution. In this article, we develop the theoretical framework for the study of such effects. We then examine the simple case where both the mobility and the diffusion coefficient are field-independent; in particular, we demonstrate that resolution can be severely reduced if the inner walls are not flat, and that optimal resolution is always obtained for perfectly flat walls. Generalized to ultrathin gels, our results clearly indicate that both random and systematic variations of the gel thickness can greatly affect the performance of the separation process. Acceptable degrees of flatness are estimated for both geometries. This study thus provides a quantitative understanding of the type of quality control one requires to obtain optimal results with capillaries and ultrathin gels.
We calculated the longitudinal and transverse diffusion coefficients for a DNA molecule undergoing gel electrophoresis in the limit where it is reptating through a dense polymer matrix. Our results indicate that both diffusion coefficients increase with the electric field intensity. The transverse and longitudinal diffusion coefficients are roughly equal for regular field intensities, but the former dominates for the high field intensities normally used for capillary gel electrophoresis (CE). This has important implications for the optimization of CE. Our results clearly show that the naive use of the zero-field diffusion constant, the Einstein relation or the longitudinal diffusion constant when calculating the contribution of the parabolic temperature profile to band broadening may lead to large overestimates under typical CE conditions. Finally, we show that the field-dependent diffusion coefficients may be responsible for the existence of an optimal field intensity for CE, even if Joule heating is neglected.
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The manner in which increasing intracellular calcium levels lead to insulin exocytosis is not known. Possibly the signal is mediated by activation of calcium/calmodulin-dependent protein kinase II (CaM Kin II). In this work the establishment of an insulinoma cell line stably overexpressing CaM Kinase II subtype delta 2 by an ecotropic retroviral transduction system is described.
Both insulin-dependent diabetes mellitus (IDDM) and unilateral nephrectomy (UNX) are associated with an increase in the glomerular filtration rate. Glomerular hyperfiltration has been linked to intraglomerular hypertension in both conditions, although it has only been linked to the development of nephropathy in diabetes. In this study, we examined the possibility of preventing diabetic nephropathy through early dopamine (DA) prodrugs treatment and we also investigated the participation of endogenous DA in the acute functional adaptation of the remaining kidney after UNX. In an animal model of IDDM (steptozotocin-treated Wistar rats), the early increase in the glomerular filtration rate was prevented by treatment with DA prodrugs (L-dopa or gludopa), an effect which was mimicked by fenoldopam (a D1 agonist) and suppressed by carbidopa and SCH 23390 (a D1 antagonist). An increase in endorenal DA synthesis and the subsequent stimulation of vascular D1 receptors appears to prevent early glomerular hyperfiltration in diabetic rats. However, in a long-term study lasting more than one year, streptozotocin-diabetic Wistar rats (unlike to diabetic Munich Wistar rats) failed to develop overt nephropathy characterized by albuminuria and systemic hypertension. During long-term treatment of diabetic rats with L-dopa, the renal availability of DA was diminished. The acute adaptation of the remaining kidney to UNX took the form of an early transient pressor effect with a moderate increase in the glomerular filtration rate and renal blood flow, and a marked decrease in tubular sodium reabsorption. SCH 23390 suppressed the hemodynamic and tubular responses to UNX, suggesting that endogenous DA plays a key role.