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Biomedical subjects

C Neumann

Publications and source records attributed to C Neumann.

At least 109 records · Page 6Linked to original sources
PubMed1996

Clinical assessment of periodontal conditions in patients treated with nifedipine.

Calcium antagonists are widely used in treating acute and chronic coronary insufficiency disorders. A major side effect of long-term treatment is gingival hyperplasia. In the present study, 70 patients taking nifedipine for at least six months and 70 controls similar in age, gender, approximal hygiene and systemic disease with at least 6 anterior teeth in upper and lower arches were examined. Their periodontal conditions were determined by modified Sulcus-Bleeding-Index (mSBI), modified Approximal-Plaque-Index (mAPI), Community Periodontal Index of Treatment Needs (CPITN), a hyperplasia index quantifying the extent of gingival overgrowth, probing depths, clinical attachment loss and the modified Phenytoin-Gingival-Inflammation-Index (mPGI). A mild to moderate gingival hyperplasia was diagnosed in 21 of 70 patients resulting in a prevalence of 30% compared to 8.5% in controls. The hyperplastic changes were situated mainly in the anterior region of the dentition. Significant differences between both groups could be found comparing the severity of the gingival hyperplasia, the CPITN, mSBI, probing depths and the part of mPGI evaluating colour and turgor of the gingiva (p < 0.05). The severity of gingival overgrowth was strongly correlated with the inflammatory gingival changes, probing depths, the periodontal treatment need and the approximal hygiene of the patients. No statistically significant correlation could be found between the severity of gingival hyperplasia and the age and gender of the patient, or the dose or duration of nifedipine therapy. Gingival changes seemed to be more pronounced in patients with cardiovascular disorders than in patients under hemodialysis. The high incidence of gingival hyperplasia in patients receiving nifedipine on a long-term basis emphasises the role of the dentist and general practitioner in the early detection and prophylaxis of gingival changes and requires a thorough information to the patient concerning periodontal side effects.

Bicuspid↗
PubMed1996

Interleukin-6 induces tyrosine phosphorylation of the Ras activating protein Shc, and its complex formation with Grb2 in the human multiple myeloma cell line LP-1.

Like many other cytokines and growth factors, interleukin-6 (IL-6) activates p21ras. However, the precise biochemical mechanisms inducing this activation are unknown. Therefore, we investigated the effects of IL-6 on some recently identified signaling intermediates, Shc (Src homology and collagen) and Grb2 (growth factor receptor bound protein 2), known to activate p21ras. In the multiple myeloma cell line LP-1, IL-6 stimulated the tyrosine phosphorylation of Shc in a time- and concentration-dependent manner. This led to the complex formulation of Shc with Grb2, an adaptor protein known to relocate a p21ras-GDP exchange factor. Sos1 (Son-of-sevenless), to the cell membrane. Taken together, these findings suggest that IL-6 might activate the Ras signaling pathway via tyrosine phosphorylation of Shc and subsequent recruitment of Grb2. Further studies will elucidate which of the IL-6 receptor associated non-receptor tyrosine kinases of the Src kinase or Janus kinase family, mediate these effects.

Adaptor Proteins, Signal Transducing↗
PubMed1996

Interleukin-13 is produced by activated human CD45RA+ and CD45RO+ T cells: modulation by interleukin-4 and interleukin-12.

Interleukin (IL)-13 is a cytokine originally identified as a product of activated T cells. Little is known however, about IL-13 production by human T cells and its modulation by other cytokines. Here, we show that IL-13 is produced by activated human CD4+ and CD8+ CD45RO+ memory T cells and CD4+ and CD8+ CD45RA+ naive T cells. In contrast, IL-4, which shares many biological activities with IL-13, is only produced by CD45RO+ T cells following activation. Analysis of intracellular cytokine production by single CD45RA+ and CD45RO+ T cells indicated that IL-13 continued to be produced for more than 24 h after stimulation, whereas IL-4 could not be detected after 24 h. These data were confirmed by measurement of specific mRNA and suggest that IL-13, unlike IL-4, but like interferon-gamma (IFN-gamma), is a cytokine with long-lasting kinetics. The majority of human CD45RO+ T cells produced IL-4 and IL-13 simultaneously. In contrast, IFN-gamma protein was generally not co-expressed with IL-4 or IL-13. IL-4 added to primary cultures of highly purified peripheral blood T cells activated by the combination of anti-CD3+anti-CD28 mAb enhanced IL-13 production by CD45RA+ and to a lesser extent by CD45RO+ T cells. Under these conditions, however, IL-12 inhibited IL-13 production by CD45RA+ T cells and to a lesser extent by CD45RO+ T cells in a dose-dependent fashion. These inhibiting effects were not related to enhanced IFN-gamma production induced by IL-12, since IFN-gamma by itself did not affect IL-13 production. Collectively, our data indicate that IL-13 is produced by peripheral blood T cells which also produce IL-4, but not IFN-gamma, and by naive CD45RA+ T cells which, in contrast, fail to produce IL-4. These observations, together with the long-lasting production of IL-13, suggest that IL-13 may have IL-4 like functions in situations where T cell-derived IL-4 is still absent or where its production has already been down-regulated.

Adjuvants, Immunologic↗
PubMed1996

Comparative analysis of the frequency of house dust mite specific and nonspecific Th1 and Th2 cells in skin lesions and peripheral blood of patients with atopic dermatitis.

Until recently it was believed that the T cell response of atopic dermatitis patients challenged with inhalant allergens originates almost exclusively and specifically from Th2 cells capable of secreting an abundance of interleukin (IL)-4 while producing no interferon (IFN)-gamma. To reevaluate this concept in a large cohort of atopic dermatitis patients we established 177 CD4+ T cell clones (45 of which showed specificity for house dust mite antigen) from the peripheral blood (n = 76), naturally occurring skin lesions (n = 40), and allergen-exposed skin (n = 61) of different patients. These clones were examined for their capacity to secrete IL-4 and IFN-gamma upon mitogenic stimulation. Moreover, 20 of these T cell clones were investigated for the synthesis of transcripts for IL-5, another Th cytokine. Our results indicate that the majority (52-100%) of allergen-specific T cells in both skin and blood of atopic individuals failed to exhibit a restricted cytokine secretion pattern and thus were classified as Th0 cells. House dust mite antigen specific T cells displaying a restricted secretion pattern (n = 16) were either of the Th1 or the Th2 type. Specific Th2 cells, however, were found almost exclusively in allergen patch test reactions, indicating that the Th2 differentiation pathway is seen preferentially in allergen-exposed skin. The cytokine secretion profile of T cell clones obtained from naturally occurring skin lesions showed similarity to those of patch test lesion, suggesting that the patch test represents a useful model to investigate the pathogenesis of atopic dermatitis.

Animals↗
PubMed1996

Human keratinocytes constitutively express IL-4 receptor molecules and respond to IL-4 with an increase in B7/BB1 expression.

In certain pathological conditions, such as atopic dermatitis, interleukin-4 (IL-4) can be detected in the skin. As the role of this cytokine in inflammatory skin lesions is not completely clear, we investigated its biological effects on skin keratinocytes. It was found that freshly isolated as well as cultured keratinocytes obtained from normal individuals express mRNA for the IL-4 receptor (IL-4R) and produce IL-4R protein, as determined by flow cytometry. Moreover, IL-4 induced a proliferative response in keratinocytes after 1 day of culture and enhanced B7/BB1 expression in these cells. B7-2 (CD86) mRNA and protein were neither detected on untreated nor IL-4 treated keratinocytes. In contrast to interferon-gamma (IFN-gamma), IL-4 did not induce ICAM-1 (CD54) or HLA-DR-expression. Keratinocytes which had been treated with IL-4 showed an enhanced ability to stimulate allogeneic T-cell proliferation in the presence of staphylococcus enterotoxin B (SEB), (p < 0.01). Neutralizing anti-B7/BB1 monoclonal antibodies did not block this effect. These results indicate that other molecules than B7/BB-1. HLA-DR or ICAM-1 on IL-4-activated keratinocytes may be involved in T-cell stimulation. In conclusion our results suggest that locally produced IL-4, besides modulating keratinocyte membrane molecules, may enable keratinocytes to interact with skin infiltrating lymphocytes.

Antigens, CD↗
PubMed1996

[A modified technic in laparoscopy-assisted appendectomy--a transumbilical approach through a single port].

The authors describe fast, inexpensive and safe technique of appendicectomy enabling them to solve majority of all patients undertaking surgery for acute or chronic inflammation. It is very careful procedure performed through one umbilical port. This method combines the advantages of the minimal invasive surgery with the safe classic way of the appendix base closure.

Appendectomy↗
PubMed1996

Adhesion molecules in atopic dermatitis: VCAM-1 and ICAM-1 expression is increased in healthy-appearing skin.

In the skin of normal and atopic individuals, the expression of E-selectin (ELAM-1), L-selectin (LECAM-1), P-selectin (CD62), CD31 (PECAM), vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1), and cutaneous lymphocyte antigen (CLA) were compared by immunostaining of skin biopsies which were taken from normal individuals (n = 17), the healthy-appearing skin of patients with atopic dermatitis (n = 10), and their acute (n = 5) and chronic (n = 6) skin lesions. In contrast to ELAM-1, the expression of VCAM-1 and ICAM-1 was found to be significantly increased in nonlesional atopic skin in comparison to the skin of normal individuals. Moreover, in contrast to normal skin of healthy individuals, nonlesional atopic skin showed a further increase of VCAM-1, ICAM-1, and ELAM-1 when cultured with medium alone. This suggests that certain adhesion molecules are constitutively upregulated in healthy-appearing skin of patients with atopic dermatitis. In addition, atopic skin appears to respond to nonspecific stimuli (such as culture with medium alone) with upregulation of VCAM-1, ICAM-1, and ELAM-1. It is suggested that the observed upregulation of adhesion molecules is mediated by the release of cytokines such as interleukin-4 from cells which reside in atopic skin. The question of whether the inherent upregulation of adhesion molecules in atopic skin contributes to the development of Th2 cells, which have been found to predominate in atopic inflammation, has to be further investigated.

Biopsy↗
PubMed1996

The sweat of patients with atopic dermatitis contains specific IgE antibodies to inhalant allergens.

We have investigated levels of total and specific IgE against inhalant allergens in the sweat of 15 patients with atopic dermatitis, 10 patients with allergic rhinitis and high levels of specific IgE in the serum, and five patients with psoriasis without atopy as controls, by means of various commercial methods such as fluorescence immunoassay, nephelometry, chemiluminescence assay, enzyme immunoassay and the radioallergosorbent test. Total IgE and specific IgE antibodies were detectable in the sweat of patients with atopic dermatitis as well as of patients with allergic rhinitis alone. These levels of total IgE in the sweat correlated with the severity of the skin disease (P < 0.05). By means of the Ciba Corning assay (P < 0.001), the fluorescence immunoassay (P < 0.05) and the nephelometry assay (P < 0.05), positive correlations were then established between the levels of total IgE in the serum and the sweat. Moreover, specific IgE antibodies to birch pollen and Dermatophagoides pteronyssinus were detectable in the sweat and correlated positively with these specific IgE levels in the serum (P < 0.05). Further, the specific IgE levels against these allergens in the sweat also correlated with the severity of dermatitis (P < 0.05). It is suggested that these specific IgE antibodies against certain inhalant allergens in the sweat of patients with atopic dermatitis may play a role in allergen trapping in the skin.

Adolescent↗
PubMed1995

Interleukin-4 and interleukin-5 are rarely co-expressed by human T cells.

Interleukin (IL)-4 and IL-5 are two cytokines which synergize in the induction of several biological effector functions. They are produced by mouse and human T helper 2 (Th2) and T helper 0 (Th0) cells. Little is known about the regulation of the two cytokines at the single-cell level. Here we show, using a flow cytometric intracellular staining technique, that IL-4 and IL-5 are predominantly produced by different human peripheral CD4+ and CD8+ T cells, whereas interferon (IFN)-gamma and IL-2 are produced by the same cells. In contrast, cloned human Th0 and Th2 cells were able to produce IL-4 and IL-5 simultaneously. The segregation of IL-4 and IL-5 in activated peripheral T cells was found within 72 h of activation upon anti-CD3 or phorbol ester + ionomycin stimulation. The kinetics of IL-4 and IL-5 production were different at the mRNA and the intra- and extracellular protein level, indicating that the cytokines are regulated differently. T cells from three patients with hyper-IgE syndrome did not display a substantial proportion of IL-4/IL-5 double-positive cells. However, simultaneous production could be induced in normal human T cells after prolonged stimulation with a minimum of two restimulation cycles. We conclude that the simultaneous production of IL-4 and IL-5 is a feature of repetitively activated human T cells.

Base Sequence↗
PubMed1995

Interleukin 5 expressing allergen-specific T-lymphocytes in patients with house dust mite sensitization: analysis at a clonal level.

Interleukin 5 (IL-5) is a T-cell lymphokine known to stimulate development, functional activity, and in vitro survival of eosinophils. Tissue and blood eosinophilia occurring during allergic responses of the immune system are potentially mediated by IL-5 secreting T-cells. To test this hypothesis a series of allergen-specific T-cell clones were established from peripheral blood and skin lymphocytes of patients with atopic dermatitis and house dust mite sensitization. In addition, alloreactive T-cell clones were also prepared from peripheral blood lymphocytes of healthy donors. Cloned T-cells were analyzed for IL-5 mRNA expression and IL-5 secretion by means of in vitro gene amplification using the reverse transcriptase polymerase chain reaction and IL-5 specific oligonucleotide hybridization, as well as IL-5-specific ELISA. A majority of allergen-specific long-term cultured T-cell clones (84%) of different donors and of either phenotype (CD8+ or CD4+) disclosed IL-5 transcripts on stimulation with lectins. Almost all clones exhibiting IL-5 transcripts also released immunoreactive IL-5 protein into their culture supernatants. In contrast, only 2% of alloreactive T-cell clones obtained from healthy donors and none of alloreactive T-cell clones of one atopic patient investigated expressed detectable amounts of IL-5 mRNA in response to lectin stimulation, all of whom were CD4+. These results suggest that eosinophilia observed in allergic responses in the peripheral blood and in tissues at the site of induced late-phase cutaneous reaction may be associated with IL-5 release by allergen-specific T-cells.

Animals↗
PubMed1995

Nocturnal oxygen desaturation in diabetic patients with severe autonomic neuropathy.

The aim of the study was to assess whether diabetic patients with autonomic neuropathy suffer from arterial oxygen desaturation during sleep. Two groups of subjects were evaluated: group I consisted of 12 patients with cardiovascular autonomic neuropathy (five with insulin-dependent diabetes mellitus (IDDM) and seven with non-insulin-dependent diabetes mellitus (NIDDM)). Group II consisted of 8 healthy subjects. Age, percentage male and body mass index (BMI) were similar in both groups. Exclusion criteria were abnormalities in arterial gas measurements, chest X-ray, spirometry or the presence of cardiac arrhythmias, obesity, uremia, alcohol abuse and use of drugs other than insulin and oral hypoglicemic agents. The results of arterial oximetry when the subjects were awake showed no differences between the two groups. However, during sleep, diabetics with autonomic neuropathy had an increased number of desaturation episodes under 85% and those episodes were more prolonged. The results suggest that diabetics with autonomic neuropathy might have abnormal control of respiration that is apparent only during sleep.

Adult↗
PubMed1995

Proliferative diabetic retinopathy is related to cardiovascular autonomic neuropathy in non-insulin-dependent diabetes mellitus.

The aim of the study was to define the relationship between the presence of proliferative diabetic retinopathy and nephropathy with objectively defined autonomic neuropathy in non-insulin-dependent diabetes mellitus (NIDDM) patients. The research design used was a cross-sectional, case control study. A cohort of NIDDM patients was classified, according to five cardiovascular autonomic tests described by Ewing, as: (1) no involvement--no abnormal tests (n = 17); (2) cardiovascular autonomic neuropathy--two out of five abnormal tests (n = 18). Age, age at diagnosis, plasma creatinine, fasting plasma glucose, glycated haemoglobin and blood pressure measurements were not statistically different among the two groups. According to indirect ophthalmoscopy and the presence of macroproteinuria and microalbuminuria, respectively, patients were also classified as having proliferative, non-proliferative or no retinopathy and with or without nephropathy. The results showed a striking relationship between cardiovascular autonomic neuropathy and proliferative diabetic retinopathy. Relative odds for nephropathy, non-proliferative diabetic retinopathy and proliferative retinopathy were, respectively, 16.0, 10.1 and 34.7. When odds ratios were adjusted for the presence of nephropathy, hypertension, non-proliferative and proliferative retinopathy, only proliferative retinopathy was significantly associated (odds ratio, 7.1). It was concluded that in NIDDM the presence of cardiovascular autonomic neuropathy is strongly associated with proliferative retinopathy. Long-term prospective studies on large cohorts of patients must be done to evaluate if having autonomic dysfunction would be a risk factor or a risk indicator of an etiologic process underlying the development of proliferative retinopathy.

Adult↗
PubMed1995

Relationship between the degree of cardiovascular autonomic dysfunction and symptoms of neuropathy and other complications of diabetes mellitus.

A cross-sectional study was designed to identify a relationship between the presence of symptoms usually related to nervous system involvement as well as other chronic complications of diabetes with three objectively defined degrees of autonomic neuropathy (AN). Symptoms usually related to peripheral sensitive neuropathy and AN were assessed using a questionnaire applied to 132 diabetics (38 IDDM and 94 NIDDM), 65 without and 67 with AN. AN was classified as follows according to 5 cardiovascular autonomic tests described by Ewing: 1) early involvement-1 abnormal test (N = 27); 2) definite involvement-2 or 3 abnormal tests (N = 26); 3) severe involvement-4 or 5 abnormal tests (N = 14). A statistically significant association was observed between degree of autonomic involvement and the presence of the following symptoms: dizziness on standing, dysphagia, vomiting, diarrhea, fecal incontinence, gustatory sweating, urinary retention, numbness and hyperesthesia of the feet or legs. Constipation and cystitis were not significantly related to cardiovascular AN. Only 3% of the patients without neuropathy and with early involvement had four or more than four of the symptoms. The prevalence of proliferative retinopathy and nephropathy was increased among patients with more severe degrees of AN. For IDDM patients there was a positive correlation between the degree of cardiovascular AN and the duration of diabetes. We conclude that: 1) severe cardiovascular AN is usually related to 4 or more of the evaluated symptoms and those patients usually have the other complications of diabetes; 2) severe AN could be a risk factor or an indicator of the same underlying process that determines the beginning of proliferative retinopathy and/or nephropathy.

Adolescent↗
PubMed1994

Pharmacological characterization of a serotonin receptor involved in an early embryonic behavior of Helisoma trivolvis.

In contrast to the abundance of information on the many physiological and developmental actions of serotonin in molluscan nervous systems, comparatively little is known about the serotonin receptors involved in these responses. Embryos of the pulmonate gastropod, Helisoma trivolvis, display a cilia-driven rotational behavior that is regulated by endogenous serotonin. In the present study, two functional assays were used to determine some of the pharmacological properties of the receptors that mediate the cilio-excitatory action of serotonin. Time-lapse video microscopy was used to measure whole embryo rotation rate and cilia beat frequency in isolated cells. In dose-response experiments, serotonin was approximately 10 times more potent in stimulating cilia beat frequency over embryo rotation. In rotation experiments, 5-carboxyamidotryptamine and methysergide had effective agonist activity in dose ranges similar to that of serotonin (1 to 100 microM). In contrast, 8-hydroxydipropylaminotetralin HBr (8-OH-DPAT) displayed agonist activity of lower potency and effectiveness. Several compounds displayed antagonist activity in the 1 to 100 microM dose range, including mianserin, spiperone, ritanserin, 1-(1-naphthyl)piperazine, and propranolol. alpha-Methylserotonin had mixed agonist-antagonist activity, and metoclopramide, MDL-72222, and ketanserin were inactive. Experiments on isolated cells suggested that the extremely effective antagonism displayed by mianserin in the embryo rotation assay was due to its specific activity at ciliary serotonin receptors. These results implicate the presence of a novel serotonin receptor on embryonic ciliated cells that is pharmacologically distinct from those previously characterized in vertebrate or invertebrate systems.

Animals↗
PubMed1994

IL-10 secretion of allergen-specific skin-derived T cells correlates positively with that of the Th2 cytokines IL-4 and IL-5.

In atopic individuals, allergen-specific CD4+ T lymphocytes often belong to the T-helper 2 (Th2) subset as they secrete the marker cytokines interleukin-4 (IL-4) and IL-5 but not interferon-gamma (INF-gamma). IL-10 is a cytokine the production of which, in the mouse system has been described to be restricted to the Th2 subset, but in the human was found to be produced by both Th1 and Th2 T cell clones (TCC). We have recently shown that house dust mite antigen (Dermatophagoides pteronyssinus)-specific TCC isolated from skin of patients with atopic dermatitis have a more polarized Th2 cytokine production profile than TCC obtained from the peripheral blood of these patients. In this study, we report that skin-derived TCC secrete more IL-10, IL-4 and IL-5, than TCC isolated from the blood of the same individual (p < 0.05). The difference was more significant with specific TCC than with non-specific TCC. Furthermore, there was a positive correlation between the production of IL-10 and that of IL-4 and IL-5, respectively. In addition, the amount of IL-4 and IL-5 secreted by specific TCC from the skin correlated positively. These results were confirmed by the detection of mRNA by PCR. Finally, our data confirm that in human blood-derived TCC IL-10 secretion is not related to a particular cytokine production profile. We suggest that the skin of AD provides an unique environment for the development of aTh2-like secretion pattern not only with respect to IL-4 and IL-5 but also regarding IL-10.

Allergens↗
PubMed1994

Maternal body mass index and pregnancy outcome in the Nutrition Collaborative Research Support Program.

This paper uses data from the Nutrition CRSP in Egypt, Mexico and Kenya to examine relationships between maternal BMI and pregnancy outcome. Women were studied from the periconceptional period up to 6 months of lactation. No women in Egypt or Mexico, and only two in Kenya where periods of food shortage occurred, had a BMI < 18 at conception. Women with a lower BMI in Mexico and Kenya gained more weight and fat in pregnancy and lost more weight and fat during lactation. These counter-intuitive relationships affect the interpretation of weight and body composition measures used to assess energy adequacy during pregnancy and lactation. Lower pre-pregnancy BMI predicted lower infant weights at birth and was a risk factor for low birthweight in Kenya. At 3-6 months post partum, maternal BMI was less strongly related to infant size, and the lean body mass component of BMI appeared to be a more important predictor than fatness.

Adult↗
PubMed1993

Primary cutaneous CD30-positive large cell lymphoma: definition of a new type of cutaneous lymphoma with a favorable prognosis. A European Multicenter Study of 47 patients.

BACKGROUND: CD30 (Ki-1)-positive anaplastic large cell lymphoma (LCL) has been described as a morphologically distinct group of LCL that generally are associated with a poor prognosis. Recent studies indicate that these lymphomas, when confined to the skin, have a favorable prognosis. However, there is no consensus regarding the definition of these primary cutaneous CD30-positive LCL. Reported patients have been selected variously on the basis of morphologic (anaplastic cytology) or immunophenotypical (expression of CD30 antigen) criteria. METHODS: At two recent workshops aimed to achieve consensus on the definition and terminology of these lymphomas, the clinical, histologic, and immunophenotypical data of 47 patients with primary cutaneous CD30-positive LCL from five collaborating European centers were analyzed. RESULTS: Characteristic clinical features were presentation with solitary or localized skin lesions (42 of 47 patients), frequent cutaneous relapses (15 patients), and partial or complete spontaneous remission of skin lesions (11 patients). Twelve of 47 (25%) patients developed extracutaneous disease. The favorable prognosis of these lymphomas is indicated by the follow-up data that show that 36 of 47 patients are alive and in complete remission, only four disease-related deaths have occurred, and the overall median survival is 42 months (range, 2-130 months). There were no differences in clinical presentation, course, or prognosis between anaplastic and nonanaplastic CD30-positive LCL. CONCLUSION: The results of this study indicate that primary cutaneous CD30-positive LCL, regardless of their morphologic classification (anaplastic or nonanaplastic) can be considered as a distinct type of cutaneous T-cell lymphoma. Recognition of this type of cutaneous lymphoma is important because it may prevent patients from unnecessary aggressive treatment.

Adolescent↗