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E Paul

Publications and source records attributed to E Paul.

At least 19 recordsLinked to original sources
PubMed1992

The anti-DNA-associated idiotype 8.12 is encoded by the V lambda II gene family and maps to the vicinity of L chain CDR1.

The 8.12 idiotype is an anti-DNA-associated Id present on lambda L chains that are expressed at high titers in 50% of patients with systemic lupus erythematosus. Since this Id can be present on as much as a third of a patient's anti-DNA antibodies and is found in renal glomeruli, 8.12 is thought to be a marker for a subset of pathogenic anti-DNA auto-antibodies. A molecular analysis of the 8.12 positive antibodies was designed to explore the genetic basis of this Id. Monoclonal human B cell lines were generated by transformation with EBV and lambda L chain-secreting lines were analyzed for Id expression and V region gene usage. In this panel of Ig lambda cell lines, the 8.12 idiotype is encoded exclusively by members of the V lambda II gene family. The sequences of several 8.12+ and 8.12- V lambda II genes are reported here and are used to map the 8.12 Id to the vicinity of CDR1, as well as to further characterize the large and polymorphic V lambda II gene family.

Amino Acid Sequence↗
PubMed1992

Purification and characterization of the apical plasma membrane of the rat pancreatic acinar cell.

A method is described for the rapid purification of the apical plasma membrane from the rat pancreatic acinar cell. It makes use of wheat germ agglutinin affinity chromatography to selectively bind vesicles with N-acetyl glucosamine present at their surface. Particular conditions (150 mM NaCl) had then to be used to keep membrane vesicles in the coveted orientation, i.e. as right-side-out vesicles. Due to its specific apical location in many epithelial cells, gamma-glutamyltranspeptidase was chosen to monitor the purification procedure. The final fraction was enriched in gamma-glutamyltranspeptidase by a factor of 75 relative to the homogenate. Na,K-ATPase, a strict basolateral membrane marker, was not detectable in the fraction. No membranes originating from other compartments, more particularly expected from zymogen granules, or from other cell types, did contaminate the preparation. As expected for an epithelial cell apical plasmalemma, lipid composition showed a very high ratio of glycolipids (37.5%). The absence of membrane-bound GP-2, and the exceptionally high specific activity of gamma-glutamyltranspeptidase suggest that the apical membrane would not be made up by the exocytosis of secretory granule, but instead by the fusion of specialized secretory vesicles very likely originating from the constitutive secretory pathway. In conclusion, this report describes a method of obtaining a fraction highly enriched in the secretory apex of the pancreatic exocrine cell that would be directly involved in exocytosis with zymogen granules and also in local anion transport.

Animals↗
PubMed1992

The role of somatic mutation in the pathogenic anti-DNA response.

Anti-DNA antibodies represent a significant autospecificity in systemic lupus erythematosus because they are essentially diagnostic of the disease and they contribute to renal pathology. The molecular genetic characterization of these antibodies from both lupus-prone mice and humans with lupus has shown them to be somatically mutated. In many cases the nature of the mutations suggests that DNA or some structurally homologous molecule is driving the response. In other cases the high replacement-to-silent mutation ratio in framework regions of the antibody suggests selection by idiotype or by some mechanism other than antigen itself. Current studies of immunoglobulin variable region genes encoding anti-DNA antibodies reveal no disease associated polymorphisms. There are also no data suggesting that the nature of the recombination process that forms intact variable region genes or of the process of somatic mutation differs in autoimmune and nonautoimmune strains or kindred. Current data suggest, rather, that a defect in regulation is responsible for auto-antibody production in SLE. The finding that most if not all anti-double stranded DNA antibodies are somatically mutated suggests the defect is in maintenance of peripheral rather than central tolerance.

Animals↗
PubMed1992

[Quantitative studies of congenital and acquired nevus cell nevi].

A total of 576 melanocytic naevi routinely excised within 1 year were analysed histologically and epidemiologically without knowledge of the clinical diagnosis. Classification into congenital melanocytic naevi (CMN, n = 82) and acquired melanocytic naevi (AMN, n = 494) was performed on the basis of the clinical history. Only a few CMN, and also some AMN, reached the lower dermis and the subcutis. An affinity of naevus cells (NC) for skin appendages was observed significantly more often in CMN than in AMN. However, no type of skin appendages was exclusively infiltrated by NC of CMN. The NC affinity for different types of skin appendages in a single naevus was characteristic of CMN. A subepidermal zone poor in NC was seen more often in CMN. The broad horizontal layer of NC within the upper dermis was rather rare in both types of melanocytic naevi. In spite of significant histological differences between CMN and AMN, the specificity and sensitivity of each criterion proved to be too low for a reliable histological diagnosis of CMN.

Adult↗
PubMed1992

[Behavior and attitude regarding skin cancer prevention and early detection in relation to current knowledge--studies of visitors to an industrial fair].

During the course of the 42nd International Trade Fair 1990 in Munich a total of 1245 visitors were interrogated with regard to their education in the early recognition of skin cancer, and their behaviour in respect of exposure to sunlight. The same persons were also subjected to melanoma screening, both with regard to special assessment of pigment lesions and inspection of the entire skin. The questionnaire showed that women were better informed than men. Approximately 87% of the questioned women had heard of the problems of melanoma, whereas only about 55% of the men belonged to the informed group. The knowledge of cancer education proved to be above average in the age group between 30 and 60 years. Persons with ample knowledge on melanoma education demonstrated more motivation to take part in cancer prevention examinations and also in examinations relating to other organ systems. Thus, the necessity of cancer screening examinations was substantially more often a matter of course among women than among men. The occurrence of skin cancer on the own body as well as its occurrence in members of one's own family does not guarantee essential knowledge on melanoma education, although in the informed group the percentage of persons directly or indirectly affected by melanoma, was higher. With regard to the behaviour towards sunlight, young people dealt more cautiously and consciously with the sun than those aged 45 and over who had exposed themselves to sunlight without exercising any caution, especially in the past.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

[Circulating CD8 as an indicator of inflammatory rheumatic disease].

An enzyme-linked immunoassay detecting soluble CD8 (s-CD8) was applied to study activation of CD8(+)-(suppressor/cytotoxic) T-cells in patients with rheumatic diseases. Compared with normals, s-CD8 levels were elevated in patients with rheumatoid arthritis, ankylosing spondylitis, and polymyositis. In contrast, low s-CD8 values were observed in patients with progressive systemic sclerosis/scleroderma. In systemic lupus erythematosus (SLE), s-CD8 values were correlated with C-reactive protein. This finding and an association with other parameters of clinical activity were confirmed by longitudinal studies. In summary, our findings support the view that implication of CD8(+)-T-cell activation is different in the pathogenesis of each rheumatic disease. Elevated s-CD8 indicates active disease, and can be used to monitor CD8(+)-T-cell activation in SLE while determination of s-CD8 seems to be of little clinical value in the other rheumatic diseases studied.

Adult↗
PubMed1992

[Epidemiology and prognosis of subungual melanoma].

Among a total of 2038 cases of malignant melanoma, 42 tumours (approximately 2%) were located sub- and periungually. The matrices of thumbs and halluces were primarily affected. Girls and women were more frequently affected than boys and men, and a broad "pyramid of age" was obvious. The mean age for both sexes was 61 years. A mean of 1.5-2 years elapsed between the appearance of the first symptoms and establishment of a definitive diagnosis. Pigmented tumours were recognized earlier than non-pigmented ones. The prognosis in melanoma of the nail has usually been found to be poor. The curves for both survival and recurrences display an initial steep downward course. A flatter course is noted for the survival curve beyond 24 months postoperatively and for the survival curve beyond 48 months after surgery. The 5-year disease-free survival rate following operative removal of the tumour or amputation of the digit is 0.50% for subungual melanoma of the hand and 0.31% for subungual melanoma of the foot. By 10 years after operative removal of the tumour, 43% of the patients with subungual melanoma of the feet are still free of disease. Similar differences are found in the length of survival. The 5-year survival rate is 0.57 for subungual melanoma of the hand and 0.48 for melanoma of the foot. The 10-year survival rates, however, are 0.41 and 0.22, respectively. Significant differences between hand and foot cannot be verified in the rate of subungual melanoma.

Adult↗
PubMed1991

Characterization of the human Ig V lambda II gene family and analysis of V lambda II and C lambda polymorphism in systemic lupus erythematosus.

We report the cDNA sequence of an expressed human V lambda II gene and present an RFLP analysis of the Ig gene family defined by this clone. This V lambda II gene was expressed in a monoclonal B cell line generated from a patient with SLE by transformation with EBV. The encoded lambda L chain displays the 8.12 Id, an Id common to anti-DNA antibodies from patients with SLE. Using a coding region probe we estimate from Southern blot analysis that the germline V lambda II gene family contains at least 15 members. Many of the V lambda II restriction fragments are polymorphic both in SLE patients and in nonautoimmune individuals. EcoRI, HindIII, and TaqI RFLP analyses of the V lambda II gene family and EcoRI analysis of the C lambda gene family reveal no polymorphisms specific to SLE. Observed V lambda II and C lambda allele frequencies are the same among SLE patients and nonautoimmune individuals, and show no evidence of linkage disequilibrium between the two loci.

Alleles↗
PubMed1991

In resting conditions, the pancreatic granule membrane protein GP-2 is secreted by cleavage of its glycosylphosphatidylinositol anchor.

GP-2 is the major membrane protein of the exocrine pancreatic secretory granule. It is an integral protein which is anchored by a phosphatidylinositolglycan. In addition to being present in the soluble contents of the granule, GP-2 is also actively secreted by the pancreas. Although 93% of the GP-2 in the resting secretions of anaesthetized rats could be pelleted, Triton X-114 phase extraction showed that 70% of this GP-2 had lost its hydrophobic properties. Proteases have been postulated to release GP-2 from the membrane, but phospholipases also have the capacity to release the protein from the membrane by hydrolysis of its peculiar glycosylphosphatidylinositol membrane anchor. These studies show the presence of inositol 1,2-(cyclic)monophosphate on the secreted hydrophilic GP-2, confirming the involvement of an endogenous phospholipase C in the solubilization of GP-2 by the exocrine pancreas. It is therefore concluded that most of the GP-2 secreted by the pancreas of anaesthetized rats under resting conditions is released from the membrane by a phospholipase C which hydrolyses the phosphodiester bond linking GP-2 to its diradylglycerol anchor.

Animals↗
PubMed1991

[Treatment of pruritic skin diseases with loratadine. Results of an open multicenter study].

Within the framework of a field study, Loratidine (Lisino) was administered to a total of 5,806 patients suffering from pruritic dermatological disorders, i.e. urticaria, neurodermatitis and eczema. As a guideline for the duration of the treatment, a period of three weeks was selected; however, many patients showed a response in a shorter time. The standard dose of loratidine was one 10-mg tablet a day. At the end of the treatment period, 69.6% the urticaria patients were free from pruritus, and 77.6% were free from wheals. In the case of the eczema patients, 47.6% were pruritus-free, while the remaining patients all showed some improvement. In the majority of cases pruritus decreased appreciably after only one hour, but at the latest on the first day of treatment. Treatment with loratidine was tolerated without side effects by 5,593 patients (96.3%).

Adolescent↗
PubMed1991

[Treatment of recurrent herpes labialis using a herpes simplex Type-I subunit vaccine. A prospective randomized double-blind multicenter study].

A herpes simplex type I subunit vaccine developed by Behring-Werke (Marburg/Lahn, FRG) was compared with placebo for therapeutic effectiveness in the treatment of recurrent orolabial herpes simplex in a multicentre study involving the major hospitals in Frankfurt/Main (n = 34), Hamburg (n = 18), Giessen (n = 17) und Kassel (n = 14). The effectiveness of the vaccine was judged on the reduction in the frequency of recurrences. Within the period of the 8-month study there was no statistically significant difference in the frequency of recurrences with vaccine or placebo. Both placebo and verum led to a significant decrease in the number of recurrences of orolabial herpes simplex, but the effect of placebo was slightly more pronounced.

Adult↗
PubMed1991

[Epidemiology of urticaria diseases].

In a prospective analysis, all patients presenting with urticaria in the practices of a general practitioner and a dermatologist and at a university clinic in the course of a year were ascertained and underwent diagnostic examination according to a uniform scheme. Urticarias are common skin diseases, affecting, at a modest estimate, about 1.3% of the population. Of all the general practitioner's patients about 3% had one of the many types of urticaria. The same percentage was found in the dermatologist's practice and among the patients attending the university clinic. The incidence of the different types of urticaria differs considerably at the different levels of medical care. This may be due to the fact that the patients are referred to a specialist or to a clinic only when the diagnosis or treatment is problematic. Half the general practitioner's urticaria patients suffer from physical urticarias (this includes the minor variants that do not necessarily require medical care). In the clinic, however, only a quarter of all patients with urticaria had physical variants. Patients with chronic urticaria accumulate in clinics because they have been referred for diagnosis and therapy. Predominantly young people were affected by physical urticaria, the peak being between 10 and 40 years. Patients with chronic "endogenous" urticaria were significantly older. About 30% of all patients also had angio-oedema, at least temporarily. Isolated swelling without urticaria occurred in only 3.9% of all patients. In urticaria, there was a slight female predominance: of all patients with physical urticaria, 61.1% were female, and the corresponding figure for nonphysical types was 53.6%. An almost equal sex distribution was found in chronic urticaria (51.9% female). In our prospective study patients presenting with urticaria only as a minor symptom was also ascertained. Many minor variants of physical urticaria were seen in these patients. In the dermatological practice, urticaria was diagnosed incidentally in 6-8% of cases. In the clinic, however, 20% of the physical urticarias and 10% of the acute nonphysical urticarias were recorded as incidental findings.

Adolescent↗
PubMed1990

[Wound healing with Iruxol. Results of a multicenter study].

In a multicenter study, a total of 100 wounds in 94 patients were treated with Iruxol ointment over a period of 3 weeks. The ointment was applied to the wound surface once or twice daily. The target parameters, wound debridement, granulation and epithelialization were assessed qualitatively. The area of the ulcers was determined quantitatively and approximately. In wounds considered to be uncomplicated, the results were clearly better than in so-called problem wounds, in which the blood supply obviously played a considerable role in the healing process. Postoperatively the wounds shrank by only two-thirds, while the area of problem wounds, i.e. "skin ulcerations", was reduced by only about 46%. On the whole Iruxol ointment was well tolerated. However, in two out of 32 patients with leg ulcers treatment had to be terminated due to contact dermatitis.

Chloramphenicol↗
PubMed1990

Understanding hospital referral rates: a user's guide.

Detailed referral information from one practice was used to investigate the effect of calculating referral rates in several different ways. Referral rates for individual general practitioners should be related to the number of consultations carried out and not to the number of registered patients; for whole practices list size may be used as the denominator. Most doctors will not need to control for age and sex of patients when comparing referral rates but may need to control for case mix when comparing referral rates to individual specialties. In addition, a method is described for distinguishing systematic variation between the referral rates of individual doctors from the random variation that may arise from data based on fairly small numbers of referrals. The method indicates whether systematic variation is greater than would be expected by chance, and it can be extended to indicate whether variability in referral rates is greater in one specialty than another. Because of random variation with time a year's data may not be sufficient to allow reliable interpretation of referral rates to individual specialties, except for the largest. At present there is no known relation between high or low referral rates and quality of care. Nevertheless, if doctors are to interpret their own rates of referral they need those rates to be reliable and valid. Use of the 10 guidelines described in this paper will help to prevent unwarranted conclusions being drawn from information on general practitioners' rates of referral to hospital.

Adolescent↗
PubMed1990

Pathogenic anti-DNA antibodies in SLE: idiotypic families and genetic origins.

We have adopted an idiotypic approach to study the double stranded DNA (dsDNA) binding antibodies of systemic lupus erythematosus (SLE). Three anti-idiotypic reagents, 8.12, 3I, and F4, identify cross reactive idiotypes that are each expressed on anti-dsDNA antibodies in the sera of many patients with SLE. These idiotypic antibodies are implicated in the pathogenesis of SLE as they are present in immune complex deposits in the kidneys of patients with SLE glomerulonephritis. The autoantibody associated idiotypes are also expressed on antibodies that do not bind DNA. We are investigating the origin of the pathogenic anti-dsDNA antibodies of SLE by comparing the autoantibodies, the antibodies to foreign antigens, and the myeloma proteins that express each SLE associated idiotype. In conjunction with serological analysis of these idiotypic systems, molecular genetic studies indicate that both the 8.12 and the 3I autoantibody associated idiotypes may be germline encoded, while the F4 idiotype is generated by somatic mutation. The data further suggest that the antigenic specificity of the pathogenic anti-DNA antibodies of SLE is acquired through somatic mutation of germline immunoglobulin genes. By studying the regulation of genes capable of encoding pathogenic autoantibodies, in both SLE patients and non-autoimmune individuals, we may be able to elucidate the pathogenesis of autoimmune disease and begin to design more effective therapeutic interventions.

Antibodies, Antinuclear↗
PubMed1990

Comparative effects of loratadine and terfenadine in the treatment of chronic idiopathic urticaria.

Loratadine is a new selective peripheral histamine H1-receptor antagonist, that is orally effective, long-acting, and devoid of significant central and autonomic nervous system activity. Its safety and efficacy were evaluated in a 28-day study conducted in patients with chronic idiopathic urticaria. Patients were randomly assigned to one of three treatment groups (loratadine, 10 mg OD; terfenadine, 60 mg BID; or placebo). Evaluation of efficacy included weekly assessments of the individual disease signs and symptoms, the overall disease condition, and therapeutic response to treatment. Throughout the 28-day treatment period progressive improvement was observed in the loratadine and terfenadine treatment groups; however, at each evaluation, loratadine was significantly more effective than placebo (P less than .01) and clinically more effective than terfenadine in reducing disease signs and symptoms. Terfenadine was significantly more effective than placebo at day 7 and endpoint (last valid visit). The overall therapeutic response at the endpoint of treatment was rated as marked or complete relief of symptoms in 64%, 52%, and 25% of the patients in the loratadine, terfenadine, and placebo treatment groups, respectively. Loratadine was well tolerated and comparable to terfenadine and placebo in incidence of adverse experiences. Sedation was reported in one patient each in the terfenadine and placebo treatment groups and an anticholinergic side effect (dry mouth) in one terfenadine-treated patient. No sedative or anticholinergic side effects were observed in patients receiving loratadine. We concluded that loratadine, 10 mg, once daily is a safe and effective treatment for symptomatic relief of chronic idiopathic urticaria.

Adolescent↗
PubMed1990

Effect of the PAF antagonist BN 52021 in ovine endotoxin shock.

It has been reported that a platelet-activating factor (PAF) antagonist ONO-6240 had little effect on pulmonary hypertension and lung lymph in sheep injected with endotoxin lipopolysaccharide (LPS); consequently we evaluated a new PAF antagonist, BN 52021. Twelve adult sheep were surgically prepared for chronic study including lung lymph drainage. LPS (S. abortus equii, 36 ng/kg/h over 7 h) was then administered with (BN group) or without (control group) infusion (1 h before LPS) of the PAF antagonist BN 52021 (4 mg/kg/30 min). Comparison of the hemodynamic data between the control group and the BN group reveals an almost identical pattern. In contrast, we find differences in the pulmonary response of the two experimental groups. The early elevation of pulmonary artery pressure after LPS administration is less in the treatment group, as is the duration of pulmonary hypertension. Similarly, thromboxane levels are lower in the treated animals. The increases in lymph flow (LQ) and transvascular protein clearance (L/P X LQ) as well as the protein flux were less prominent in the treatment group. The mean lymph flow per hour was significantly higher in the control group. The mean lymph flow per hour was significantly higher in the control group, as were the corresponding parameters for clearance and protein flux. Thus the pulmonary vasculature and lung fluid balance disruption produced by LPS was markedly reduced by treatment with the PAF blocker.

Animals↗