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Biomedical subjects

E Paul

Publications and source records attributed to E Paul.

At least 19 recordsLinked to original sources
PubMed1995

Modulation of Ca2+ sensitivity in smooth muscle by genistein and protein tyrosine phosphorylation.

Genistein, a potent tyrosine kinase inhibitor, inhibits contraction of several types of smooth muscle, suggesting that protein tyrosine phosphorylation may be an important regulatory mechanism for smooth muscle contraction. We suspected that one site between activation of smooth muscle and contraction which might be modulated by protein tyrosine phosphorylation involved mechanisms for control of Ca2+ sensitivity. Since smooth muscle permeabilized with staphylococcal alpha-toxin permits direct assessment of agonist-induced Ca2+ sensitivity, we studied the effects of genistein on potential coupling between tyrosine phosphorylation and Ca2+ sensitivity in permeabilized ileal smooth muscle. Results show that contraction of intact preparations with carbachol is markedly and reversibly inhibited by 40% at 4 micrograms genistein/ml and by 60% at 20 micrograms genistein/ml. Permeabilized preparations that are contracted with a submaximal [Ca2+] in the presence of GTP relax when genistein is added to the medium. Genistein also reversibly inhibits contractions induced in permeabilized muscle with either a submaximal or maximal [Ca2+] in the presence of GTP, as well as receptor-coupled activation of Ca2+ sensitization with 10 microM carbachol/10 microM GTP. Activation of permeabilized preparations at pCa 4.6 in the presence of 100 microM GTP promotes time-dependent tyrosine phosphorylation of several substrates. Both phosphorylation and force are inhibited by genistein. However, relatively high levels of myosin light chain phosphorylation persist during genistein-induced inhibition of Ca2+ sensitivity. In contrast, genistein has no effect on Ca(2+)-activated contraction in Triton-skinned preparations in either the presence or the absence of GTP. This shows that it does not directly inhibit actin-myosin interaction and suggests that its target(s) may be a cytosolic or membrane-bound regulatory protein(s) that is leached from the preparations during Triton-skinning. Taken together, these new data suggest that (a) tyrosine phosphorylation of one or more substrates may be coupled to mechanisms which regulate Ca2+ sensitivity and (b) the inhibitory effects of genistein are probably due to inhibition of agonist-induced Ca2+ sensitivity.

Animals↗
PubMed1995

Plasma glutathione S-transferase as an early marker of posttraumatic hepatic injury in non-human primates.

We have hypothesized that the measurement of alpha-glutathione S-transferase (alpha-GST) in serum may provide a suitable sensitive marker of shock-induced liver damage. Six male adult baboons were studied. Hemorrhage was induced by blood withdrawal of 60-70% of the total blood volume down to an arterial pressure of 35-40 mmHg. Then the reinfusion was performed with the heparinized shed blood plus the same amount of Ringer's solution over the next 4 h. Before the start of hemorrhage, 2 mL/kg zymosan-activated plasma was infused to simulate trauma-related complement activation. alpha-GST antigen levels were determined using an anti-human alpha-GST immunoassay (Hepkit). Concentrations of alpha-GST at baseline in baboon were found to be 3.1 +/- 1.8 ng/mL; at the end of the shock period a significant increase in alpha-GST serum levels (74.8 +/- 13.8 ng/mL) was found. In contrast, transaminase levels did not significantly change. From the current evidence in posttraumatic non-human primates, which resemble the clinical situation in several aspects, alpha-GST measurements are a suitable marker of early hepatocellular injury.

Animals↗
PubMed1993

Variations in the distribution, frequency, and phenotype of Langerhans cells during the evolution of malignant melanoma of the skin.

We examined the frequency, distribution, and immunophenotype (S-100 protein, CD1) of epidermal Langerhans cells (LC) in the epidermis overlying primary melanoma, and dermal dendritic cells (DC) in the dermis deep to melanoma, and in adjacent normal skin. There is a substantial reduction in S-100+ LC and a lesser decline in CD1+ LC in the epidermis over melanoma. There is a simultaneous increase in the frequency of cells expressing these phenotypes in the dermis deep to tumor. Double-staining studies in progress show coexpression of S-100 and CD1 in most of these cells. The depletion of S-100+/CD1+ DC from the peritumoral epidermis is maximum in deeper (Clark level III-V) and thicker (> 0.76 mm) tumors. The reduction in total DC in peritumoral epidermis is, however, proportionally less than the reduction in S-100+/CD1+ DC owing to an increase in cells that are S-100-/CD1+. The proportion of S-100+/CD1+ dermal DC deep to tumor is similar to that in normal epidermis and dermis, suggesting that there is no increased migration of S-100-/CD1+ DC from tumor-associated epidermis to subjacent dermis. Non-dendritic leukocytes in the dermis deep to tumor were increased in frequency, maximally in the dermis deep to thinner and more superficial melanomas. Most such cells were T lymphocytes with helper/inducer cells predominating. The data presented show substantial alterations in the frequency, distribution, and phenotype of LC/DC as melanoma evolves, alterations that may be critical for development of effective tumor-directed immunity.

Antigens, CD↗
PubMed1993

Characterization of two human anti-DNA antibodies bearing the pathogenic idiotype 8.12.

Antibodies against double stranded DNA (dsDNA) are characteristic of systemic lupus erythematosus (SLE) and have been implicated in disease pathogenesis. Up to one third of an SLE patient's anti-dsDNA antibodies can express the lambda L chain idiotype 8.12. Serum titers of this idiotype are elevated in 50% of SLE patients, and idiotypic antibodies are present in glomerular immune deposits associated with lupus nephritis. Two EBV transformed B cell lines, KS3 from a patient with SLE and SD6 from an individual without autoimmune disease, secrete 8.12+ IgG antibodies that bind dsDNA. The 8.12+ lambda L chains of these anti-DNA antibodies are encoded by members of the V lambda II gene family; the KS3 heavy chain is encoded by a VH4-DM1-DQ52-JH6b-C gamma 1 gene rearrangement and the SD6 heavy chain is encoded by a VH3-D21/9-JH6b-C gamma 1 rearrangement. Both of these monoclonal antibodies are somatically mutated: the KS3 antibody displays mutations in complementarity determining regions (CDRs) and the SD6 antibody in framework regions (FRs). The significance of these different patterns of mutation in two potentially pathogenic anti-DNA antibodies is discussed.

Amino Acid Sequence↗
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↗