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Biomedical subjects

A Krause

Publications and source records attributed to A Krause.

At least 91 records · Page 5Linked to original sources
PubMed1999

Reduced catecholamine response of lymphocytes from patients with rheumatoid arthritis.

Catecholamines modulate lymphocyte function via stimulation of beta2-adrenergic receptors (beta2R). Previous investigations revealed a decreased density of beta2R on peripheral blood mononuclear cells (PBMC) in patients with chronic rheumatic diseases. Aim of the present study was to determine the impact of this decrease on catecholamine response of PBMC from patients with rheumatoid arthritis (RA) in vitro. PBMC from 17 patients with RA and 12 healthy blood donors (HD) were investigated. Beta2R were determined by a radioligand binding assay. The effects of epinephrine (E) and norepinephrine (NE) on PBMC proliferation were studied using cells activated with pokeweed mitogen (PWM) and monoclonal anti-CD3-antibodies (OKT3), respectively. In parallel, alpha1- or beta-receptor antagonist were added to the culture to determine the specificity of the catecholaminergic effects. The results showed that depending on the stimulus and the catecholamine concentration employed E and NE exert inhibitory (OKT3) or stimulatory signals (PWM) on lymphocyte proliferation. Inhibitory effects could be abolished by adding beta-antagonist, while stimulatory signals were diminished after addition of alpha1- of beta-antagonist. Patients with RA showed a significantly reduced density of beta2R compared to HD paralleled by a significantly reduced influence of catecholamines on lymphocyte function. The study demonstrates the intricate relationship between PBMC reactivity and catecholamine effects that are mediated via alpha1- and beta-adrenergic receptors. In this respect the reduced catecholamine response of PBMC from RA patients may contribute to the pathogenic process of RA.

Adrenergic alpha-Antagonists↗
PubMed1999

Phagocytosis of microorganisms by means of overshooting pseudopods: where do we stand?

During the endocytic uptake of particulate material such as microorganisms, the transition from the engulfment step to the internalization step of phagocytosis may be disturbed. Thus, the pseudopods flanking the particles do not close to a phagosome, but lie on top of each other. This uncoupling of pseudopod extension and phagosome formation provides useful information about the regular course of phagocytosis. Experimental models on the phenomena of coiling and overlapping phagocytosis have so far been established with legionellas, spirochetes, trypanosomatids, fungal cells, and zymosan.

Animals↗
PubMed1999

Cancer patient T cells genetically targeted to prostate-specific membrane antigen specifically lyse prostate cancer cells and release cytokines in response to prostate-specific membrane antigen.

The expression of immunoglobulin-based artificial receptors in normal T lymphocytes provides a means to target lymphocytes to cell surface antigens independently of major histocompatibility complex restriction. Such artificial receptors have been previously shown to confer antigen-specific tumoricidal properties in murine T cells. We constructed a novel zeta chain fusion receptor specific for prostate-specific membrane antigen (PSMA) termed Pz-1. PSMA is a cell-surface glycoprotein expressed on prostate cancer cells and the neovascular endothelium of multiple carcinomas. We show that primary T cells harvested from five of five patients with different stages of prostate cancer and transduced with the Pz-1 receptor readily lyse prostate cancer cells. Having established a culture system using fibroblasts that express PSMA, we next show that T cells expressing the Pz-1 receptor release cytokines in response to cell-bound PSMA. Furthermore, we show that the cytokine release is greatly augmented by B7.1-mediated costimulation. Thus, our findings support the feasibility of adoptive cell therapy by using genetically engineered T cells in prostate cancer patients and suggest that both CD4+ and CD8+ T lymphocyte functions can be synergistically targeted against tumor cells.

3T3 Cells↗
PubMed1999

WWW access to the SYSTERS protein sequence cluster set.

SUMMARY: We present a Web server where the SYSTERS cluster set of the non-redundant protein database consisting of sequences from SWISS-PROT and PIR is being made available for querying and browsing. The cluster set can be searched with a new sequence using the SSMAL search tool. Additionally, a multiple alignment is generated for each cluster and annotated with domain information from the Pfam protein family database. AVAILABILITY: The server address is http://www.dkfz-heidelberg.de/tbi/services/cluster/ systersform

Algorithms↗
PubMed1999

Breast reconstruction with latissimus dorsi flap: improved aesthetic results after transection of its humeral insertion.

Does transecting the tendinous insertion of the latissimus dorsi on the humerus improve aesthetic results and avoid the displeasing bulge in the armpit that sometimes occurs when the latissimus dorsi is used for breast reconstruction? In a prospective study, 60 patients who were having breast cancer surgery and simultaneous breast reconstruction using the latissimus dorsi flap were randomized for cutting (n = 29) or leaving intact (n = 31) the tendinous muscle insertion on the humerus. The cosmetic outcome was evaluated by patients and surgeons 6 to 12 months postoperatively. Patients reported good cosmetic results in 29 of 31 cases with the humeral insertion left intact and in 26 of 29 cases when the tendon was cut (p = 0.59), as compared with 21 of 31 cases versus 25 of 29 cases (p = 0.091), according to the surgeon's evaluation. A lateral bulge was more frequently observed by the surgeons in the group with intact insertion (10 of 31 patients), as compared with the group with a transected humeral insertion (2 of 29 patients). Discomfort caused by this bulge was reported by 19 of 31 patients with intact insertion, but only 3 of 29 patients with the tendon cut (p < 0.0001). The additional transection of the tendon was not associated with any complications. The additional transection of the tendinous humeral insertion of the latissimus dorsi muscle improves aesthetic results and avoids a displeasing bulge in the axilla when the latissimus dorsi flap is used for breast reconstruction.

Breast Neoplasms↗
PubMed1999

Pulmonary involvement in diffuse cutaneous systemic sclerosis: broncheoalveolar fluid granulocytosis predicts progression of fibrosing alveolitis.

OBJECTIVE: The clinical course of fibrosing alveolitis (FA) in patients with systemic sclerosis (SSc) may vary considerably from stable condition for years to continuous fatal progression. This prospective study aimed at identifying the prognostic value of bronchoalveolar lavage fluid (BALF) analysis in FASSc. METHODS: Seventy three consecutive patients with SSc and clinical signs of pulmonary involvement were enrolled. Every patient underwent clinical examination, lung function tests, computed tomography (CT), gallium scan, echocardiography, and bronchoalveolar lavage (BAL). Forty nine patients, 26 with pathological and 23 with normal BALF findings were prospectively followed up for two years and re-evaluated annually. RESULTS: At baseline, 51 subjects (70%) showed radiological signs of lung fibrosis and/or alveolitis by CT and diffusion capacity for carbon monoxide (DLco) was decreased in 47 patients (64%). Thirty five patients (48%) had pathological BALF findings. BALF differential counts included BALF granulocytosis in 18, BALF lymphocytosis in 12, and a mixed increase of both granulocytes and lymphocytes in five patients. On follow up, a progression of FA with a significant decrease of DLco was only observed in patients with BALF granulocytosis. In contrast, patients with BALF lymphocytosis or normal BALF cell count had stable lung function parameters during the study period. In none of our patients echocardiography showed evidence of pulmonary hypertension. CONCLUSION: BALF granulocytosis predicts progression of FA with deterioration of lung function, which is most sensitively monitored by DLco. Immunosuppressive treatment is recommended in patients with granulocytic FASSc.

Bronchoalveolar Lavage Fluid↗
PubMed1999

[Rating of transvaginal sonography in the evaluation of postmenopausal bleeding].

OBJECTIVE: The purpose of this study was to evaluate transvaginal ultrasonography (TVS) in differential diagnosis of vaginal bleedings in postmenopausal patients. MATERIAL AND METHODS: Between January 1990 and December 1996, 1198 postmenopausal patients with vaginal bleedings were sent to our clinic for a histological evaluation. Eight hundred and seventy-nine patients (73.4%) were preoperatively scanned by transvaginal probe, and endometrial thickness (< 5, 5-7, 8-10, > 10 mm) was measured. RESULTS: Atrophy was found in 46.3%, endometrial polyps in 19.8%, endometrial cancer in 17.5%, and hyperplasia in 6.7%. An endometrial thickness of lower than 5 mm (p < 0.0001) was shown in TVS patients with atrophy in 71%, with endometrial polyps in 10.9%, with endometrial cancer in 3.9% and hyperplasia in 6.8%. In 55.2% of these eases with endometrial cancer the preoperatively estimated thickness was 10 mm or more. The additionally morphologic examination in cases with an endometrium smaller than 5 mm was false positive in 75% (9/12). Thus an endometrial thickness of > 5 mm had a sensitivity of 92.5%, specificity of 71.0%, positive and negative predictive value of 75.6, respectively 90.9% for the detection of endometrial pathology. CONCLUSIONS: TVS allows the detection of an endometrial pathology in the vast majority of patients with postmenopausal bleedings. In cases with a single postmenopausal bleeding and an endometrium smaller than 5 mm we recommend expectative procedures with repeated ultrasound examination of the endometrium.

Aged↗
PubMed1999

Utilisation of predictive, prenatal and diagnostic testing for Huntington's disease in Johannesburg.

CONTEXT: Huntington's disease (HD) is a dominantly inherited condition in which the gene defect is known. As such individuals in at-risk families can be tested before symptoms occur, prenatally, or after symptoms appear to confirm the diagnosis. OBJECTIVES: To investigate the utilisation and sequelae of the predictive, prenatal and diagnostic services offered to families with suspected Huntington's disease. DESIGN: A retrospective design was used. The 1975-1997 records of the Department of Human Genetics for all families with a history of HD presenting for genetic counselling and DNA analysis were studied. SETTING: Department of Human Genetics, South African Institute for Medical Research and University of the Witwatersrand, Johannesburg. SUBJECTS: There were 30 at-risk (50% risk) subjects for predictive testing, 7 women (10 pregnancies) for prenatal testing, and 52 subjects for diagnostic testing. OUTCOME MEASURES: These were provided by the results from molecular studies and by the action taken by subjects after a predictive or prenatal result was given. RESULTS: Altogether 15 (50%) subjects for predictive testing had a positive result, but none had serious psychiatric sequelae. Two women were found to be carrying an affected fetus and both requested pregnancy termination. Of 52 diagnostic tests, 33 (63%) were positive. CONCLUSION: The service was used appropriately, and there were no traumatic incidents following positive results. There was no genotypic or sex bias in subjects presenting for testing. Black and white patients were equally likely to be positive for HD on diagnostic testing. The families appreciated the service and found it useful in the detection and prevention of HD.

Female↗
PubMed1998

Stress-activated protein kinase/Jun N-terminal kinase is required for interleukin (IL)-1-induced IL-6 and IL-8 gene expression in the human epidermal carcinoma cell line KB.

The cytokine interleukin-1 (IL-1) is a major inflammatory hormone which activates a broad range of genes during inflammation. The signaling mechanisms triggered by IL-1 include activation of several distinct protein kinase systems. The stress-activated protein kinase (SAPK), also termed Jun N-terminal kinase (JNK), is activated particularly strongly by the cytokine. In an attempt to delineate its role in activation of gene expression by IL-1, we inhibited the IL-1-induced SAPK/JNK activity by stable overexpression of either a catalytically inactive mutant of SAPKbeta (SAPKbeta(K-R)) or antisense RNA to SAPKbeta in human epidermal carcinoma cells. A detailed analysis of signal transduction in those cells showed that activation of neither NFkappaB nor p38 mitogen-activated protein kinase was affected, suggesting that we achieved specific blockade of the SAPK/JNK. In untransfected and vector-transfected KB cells, IL-1 induced a strong increase in expression of IL-6 and IL-8 mRNA, along with the synthesis of high amounts of the proteins. In two KB cell clones stably overexpressing the mutant SAPKbeta(K-R), and three clones stably overexpressing antisense RNA to SAPKbeta, expression of IL-6 and IL-8 in response to IL-1 was strongly reduced at both the mRNA and protein level. These data indicate that the SAPK/JNK pathway provides an indispensable signal for IL-1-induced expression of IL-6 and IL-8.

Calcium-Calmodulin-Dependent Protein Kinases↗
PubMed1998

Antigen-dependent CD28 signaling selectively enhances survival and proliferation in genetically modified activated human primary T lymphocytes.

Most tumor cells function poorly as antigen-presenting cells in part because they do not express costimulatory molecules. To provide costimulation to T lymphocytes that recognize tumor cells, we constructed a CD28-like receptor specific for GD2, a ganglioside overexpressed on the surface of neuroblastoma, small-cell lung carcinoma, melanoma, and other human tumors. Recognition of GD2 was provided by a single-chain antibody derived from the GD2-specific monoclonal antibody 3G6. We demonstrate that the chimeric receptor 3G6-CD28 provides CD28 signaling upon specific recognition of the GD2 antigen on tumor cells. Human primary T lymphocytes retrovirally transduced with 3G6-CD28 secrete interleukin 2, survive proapoptotic culture conditions, and selectively undergo clonal expansion in the presence of an antiidiotypic antibody specific for 3G6-CD28. Polyclonal CD8(+) lymphocytes expressing 3G6-CD28 are selectively expanded when cultured with cells expressing allogeneic major histocompatibility complex class I together with GD2. Primary T cells given such an antigen-dependent survival advantage should be very useful to augment immune responses against tumor cells.

Animals↗
PubMed1998

Huntington's disease confirmed by genetic testing in five African families.

Huntington's disease is an autosomal-dominant inherited progressive neurodegenerative disease associated with an expanded trinucleotide repeat (CAG) sequence on the short arm of chromosome 4. The disease is considered rare in Africans. We report five black South African families of different ethnic origin with proven expansions typical of Huntington's disease and discuss the possible origins of the disease in Africa.

Black People↗
PubMed1998

[Duplex ultrasound examinations of retinal circulation after inhalation of various mixed respiratory gases].

BACKGROUND: Hyperoxic-hypercapnic inhalation is a therapeutic option in vascular disorders of the retina. The effect of hyperoxic and/or hypercapnic inhalation on the perfusion of the retina was examined. METHODS: Twenty-five young adults between 18 and 35 years were investigated in a prospective study. They inhaled one of three different mixtures of breathing gases: (1) 100% O2, (2) Carbogen 240 (95% O2 and 5% CO2), (3) 92% O2 with 8% CO2 and were examined by color Doppler imaging of the CRA and OA before and after inhalation. The resistance index (RI) was calculated. RESULTS: The majority of the subjects showed an Increase in the RI in both ophthalmic vessels after inhalation of pure O2, a decrease after breathing in 92% O2 and 8% CO2 and it remained almost constant with inhalation of 95% O2 and 5% CO2. CONCLUSIONS: Inhalation of 92% O2 and 8% CO2 is a possibility for decreasing the peripheral resistance of OA and CRA. No change in blood flow was observed with Carbogen 240.

Adolescent↗