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Biomedical subjects

T Fischer

Publications and source records attributed to T Fischer.

At least 163 records · Page 9Linked to original sources
PubMed1998

Activation of purinergic P2Y2 receptors inhibits inducible NO synthase in cultured rat mesangial cells.

Cytokine-induced nitric oxide (NO) is produced on glomerular inflammation. Glomerular injury and thrombocyte aggregation result in the release of nucleotides, which may regulate induced NO synthesis in cultured rat mesangial cells (MCs). ATP (10(-3) M) inhibited 24-h nitrite production induced by lipopolysaccharide (LPS, 10 microg/ml)/interferon-gamma (IFN-gamma, 100 U/ml) by 48.2 +/- 6. 3%, as well as induction of inducible NOS (iNOS) protein and mRNA. Also, coincubation with either 10(-4) M of UTP, ATP, or ATPgammaS inhibited LPS/IFN-gamma-induced nitrite production by 29.9 +/- 5.8, 36.4 +/- 4.3, and 50.3 +/- 6.5%, respectively, indicating involvement of purinergic P2Y2 receptors. Correspondingly, cultured MCs expressed P2Y2 receptor mRNA. Agonists for other purinergic receptors [alpha,beta-methylene-ATP, 3'-O-(4-benzoyl)-benzoyl-ATP, 2-methylthio-ATP, ADP, UDP, adenosine] were ineffective. Treatment with the protein kinase C (PKC) activator phorbol 12-myristate 13-acetate (PMA, 10(-8) M) reproduced the inhibitory effect of ATP on iNOS protein expression and nitrite inhibition (by 46.6 +/- 10. 4%). The effect of ATP or PMA was reversed by the PKC inhibitors Ro-31-8220 (10(-8) M) and 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine (10(-5) M), indicating that suppression of iNOS is mediated via activation of PKC through stimulated P2Y2 receptors. In conclusion, the release of purine mediators may play a critical role for iNOS expression and synthesis of NO during glomerular inflammatory disorders.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1998

Evidence against elevated sympathetic vasoconstrictor activity in borderline hypertension.

The relationship between sympathetic nerve activity and BP in the early stages of essential hypertension remains unclear. To investigate this relationship further, this study measured resting muscle sympathetic nerve activity (MSNA: representing peripheral vasoconstrictor activity), plasma catecholamines, BP, central venous pressure, and heart rate in 20 young (24 +/- 2 SD yr), lean (body mass index, 24.2 +/- 3.0 kg/m2), male subjects with borderline hypertension (BHT) and in 21 male normotensive (NT) control subjects matched for age and body mass index. A cold pressor test was also performed to evaluate sympathetic reflex responsiveness. Resting mean BP and heart rate were significantly higher in the BHT subjects compared with NT subjects (113 +/- 9 versus 89 +/- 9 mmHg; 74 +/- 8 versus 62 +/- 8 bpm; P < 0.0001 each) with no difference in central venous pressure. Resting MSNA levels tended to be lower in the BHT versus the NT group (12 +/- 6 versus 14 +/- 9 bursts/min, P = NS; 16 +/- 8 versus 22 +/- 13 bursts/100 heartbeats, P = 0.05) and did not correlate with either BP or body mass index. Significant positive correlations were found between resting MSNA and plasma norepinephrine levels in both groups (P < 0.05). Hemodynamic and sympathetic nerve responses to the cold pressor test were similar between the BHT and NT subjects. It is concluded that resting MSNA and plasma norepinephrine levels are correlated in young lean NT and BHT men; however, neither of these variables is correlated with BP. Because MSNA was similar in the two groups, the concept that augmented resting MSNA is important in the early developmental phase of essential hypertension must be reevaluated.

Adult↗
PubMed1998

[Computer-assisted stress analysis in rehabilitation with ABBA (job requirements and capacity analysis)].

ABBA is a recently devised, ergology-based expert system software for vocational analysis, documentation and evaluation--inter alia in the context of medical and vocational rehabilitation-, drawing on some 20 years of experience in job analysis with the AET (Arbeitswissenschaftliches Erhebungsverfahren zur Tätigkeitsanalyse). Designed for broad and differentiated coverage, a PARADOX data bank comprising the entire data collected enables comparison of job requirements and client performance potential, reaching for beyond individual analysis on account of its integration of job profiles for a given industry or occupation, or for an entire company. The related, and easy-to use, software for data processing and appraisal is now being made available by ABBA along with dialogue-based ergological know-how.

Diagnosis, Computer-Assisted↗
PubMed1998

[Kinetics of receptor-mediated radiotoxicity of 16alpha-[125I]-iodostradiol-3,17beta].

AIM: The radiocytotoxic effects in estrogen receptor (ER) containing MCF-7 cells of a mamma carcinoma were investigated following incubation with [125I]E ranging from 1 h to 24 h. METHODS: The receptor status of the cells was confirmed by immunohistochemical staining. The accumulation of [125I]E in MCF-7 cells was tested in the presence and absence of radioinert E and [127I]E and in ER-negative cells in comparison to ER-positive cells. The subcellular distribution was investigated in 0.25 M Saccharose by ultra centrifugation. The radiocytotoxicity was assessed in ER-positive and negative cells by a standard colony forming assay after incubating with [125I]E (1.85 kBq/ml-55.5 kBq/ml) for 1, 2, 4, 8, 12, and 24 h. RESULTS: A significant cytotoxicity was observed only when ER-rich MCF-7-cells were incubated with [125I]E alone. The maximal cytotoxic effect was a reduction of survival fraction to 20-25%. This was achieved at radioactivity concentrations > 37 kBq/ml. Maximal effect was seen after 8 h incubation, extension of incubation time did not further increase toxicity. CONCLUSION: The results suggest that the radioactivity was bound to ER. Through their nuclear localization radioestrogens tagged with radionuclides emitting very low energy electrons (Auger electrons) bear potential for therapy by ER-mediated deposition of lethal doses of ionizing radiation to single cells without affecting neighbouring cells. But, instead of 125I the shorter-living 123I shall be used for labelling because the deciding radiation effectes occur within the first 8 h.

Biological Transport↗
PubMed1998

A study of new fragrance mixtures.

OBJECTIVE: To determine the frequency of responses to four mixtures of fragrance materials in routine clinic patients undergoing patch testing for suspect allergic contact dermatitis. The validity of using fragrance mixtures alone, or in combination, was evaluated in terms of predicting allergy to fragrance judged on the basis of finding a response to at least one of the fragrance mixtures. METHODS: A total of 752 subjects were patch tested in five centers worldwide with (1) fragrance mix 8% (FM), (2) balsam of Peru 25%, (3) a mixture of seven of the eight FM 8% ingredients and other fragrance ingredients including jasmine absolute (jasmine/FM mix), and (4) a mixture of five selected natural fragrance ingredients (NM). RESULTS: Of 752 subjects, 100 (13%) had positive patch tests to at least one of the four fragrance mixtures. The age of the patients was 45.2 +/- 18.3 years (mean +/- SD). Ninety-six percent were Caucasian. Facial eruptions and hand involvement were the most common topographic sites. Of subjects exhibiting a positive response, 67% reacted to FM, 63% to the jasmine/FM mix, 47% to the NM, and 38% to balsam of Peru. Testing with FM and NM identified 84% of the perfume-allergic patients. FM 8% tested simultaneously with the jasmine/FM mix identified 86% of the perfume-allergic patients. Testing simultaneously with three test materials combining either the NM or the jasmine/FM mix with balsam of Peru and FM identified 95% of the perfume-sensitive patients. CONCLUSIONS: The simultaneous testing of NM or jasmine/FM mix, in addition to the conventional use of FM 8% and balsam of Peru, increases the sensitivity of testing for fragrance allergy from 81% to 95%.

Balsams↗
PubMed1998

Visual and laser Doppler perfusion scanning assessments of Kathon CG patch test reactions.

BACKGROUND: Testing procedure for Kathon CG (Diagnostics AB, Tygelsjö, Sweden) is not standardized. OBJECTIVE: To improve test results for Kathon CG. METHODS: Eleven subjects were tested with Kathon CG patch tests applied from 6 to 96 hours. Tests were read visually and by a laser Doppler perfusion scanning technique at time points ranging from 6 to 240 hours. RESULTS: There were large differences in the perfusion profiles of subjects tested in identical fashion. Beginning reactions were detected earlier with the laser Doppler scanning than with the visual assessment technique. There was no obvious agreement between peak perfusion values of reactions and application times. Both assessment techniques were effective at distinguishing between positive and negative subjects at an adequate dose and application time. This distinction was possible using a shorter reading time with the laser Doppler scanning for all subjects. Six-hour applications were sufficient to detect all positive subjects so tested regardless of assessment technique. With that application time, positive and negative subjects were most effectively identified using long reading times regardless of assessment technique. CONCLUSION: The shortest application time used on all subjects, 24 hours, was effective and 6-hour applications with long reading times for all subjects so tested. Doses lower than 0.0040 mg/cm2 resulted in false-negative tests.

Adult↗
PubMed1997

Evidence for a CD4-associated calcium influx independent of the phosphoinositide transduction pathway in human T cells.

We recently showed, using human Jurkat T cell variants lacking the T cell receptor (TCR)/CD3 complex, that the lectin jacalin is able to trigger intracellular calcium increase provided that CD4 is expressed on the cell surface. Involvement of the CD4 molecule in jacalin-induced biological effects was furthermore demonstrated in differentiated U937 myelomonocytic cells expressing or not expressing CD4, and is confirmed here in human CD4-transfected mouse thymoma cells. In the present paper, we analyze the CD4-associated calcium response triggered by jacalin independently of the TCR/CD3 complex. We show that the observed calcium rise results from a direct long-lasting calcium influx from the outside without release of calcium from intracellular stores. We demonstrate that it is independent of the phosphoinositide phospholipase C transduction pathway. Moreover, we show that this peculiar calcium response can be blocked by protein tyrosine kinase inhibitors (herbimycin and genistein) giving evidence of the involvement of a protein tyrosine kinase, the best candidate of which is the CD4-associated p56lck. Altogether, our results suggest that, independently of the TCR/CD3 complex, CD4 may be involved in the triggering of a calcium signal dependent on a protein tyrosine kinase and independent of the phosphoinositide transduction pathway.

Animals↗
PubMed1997

Optimising assay sequence on automated coagulation instrumentation.

An embedded knowledge-based system has been developed to determine the optimum sequence for assays performed on a random access coagulation analyser. This knowledge base is in the form of a set of rules describing penalties associated with certain sequences of assays. The optimisation of assay sequences increases throughput and reduces consumption of cleaning solutions and generation of waste. A flexible design also facilitates updates to the knowledge base as assays are modified and added in the future.

Artificial Intelligence↗
PubMed1997

New method for monitoring the functional state of a dynamic cardiomyoplasty.

OBJECTIVE: To assess the impact of a dynamic cardiomyoplasty on failing hearts, it is essential to estimate the contraction force of the skeletal muscle and how its contraction is synchronized with the heart cycle. METHODS: In a 6-month study a small fluid-filled, balloon-mounted catheter was placed between the myocardium and the muscular wrap in five adult female Boor goats and two female domestic pigs. The catheter was connected to a subcutaneous measuring chamber whereby pressure monitoring could be accomplished. Distinct pressure signals as a result of function of the dynamic cardiomyoplasty and the heart were detected initially in all animals. RESULTS: Maximal relative pressure from the dynamic cardiomyoplasty was calculated as 336.2% +/- 69.4% on day 24 +/- 6.1 (n = 7) and end-stage pressure as 59.8% +/- 9.7% on day 174.6 +/- 13.1 (n = 4). A functional loss of pressure signals from the dynamic cardiomyoplasty was correlated to severe histologic muscle damage (n = 3). Pressure signals transferred from the contracting myocardium to the catheter showed defined segments of contraction, ejection, and filling periods, allowing a mechanical synchronization of the dynamic cardiomyoplasty to the heart cycle. CONCLUSIONS: This monitoring catheter enabled the assessment of the functional state of the dynamic cardiomyoplasty and allowed a synchronization to the heart cycle. It will promote understanding and might help to avoid muscle damage in dynamic cardiomyoplasty for an improved outcome of the surgical treatment of end-stage heart failure.

Animals↗
PubMed1997

Rise and fall of caries prevalence in German towns with different F concentrations in drinking water.

The rise and fall of caries prevalence (DMFT) and its relation to changing F concentration of drinking water and other health-related factors is analysed based on dental findings of more than 286,000 subjects of either sex (6-15 years old) from the two industrial towns Chemnitz and Plauen. Water fluoridation (1.0 +/- 0.1 ppm F) was implemented in Chemnitz (formerly Karl-Marx-Stadt) in 1959. It was in operation until autumn 1990 with an interruption lasting 22 months around the year 1971. In the F-poor town of comparison, Plauen, 55% of the citizens were supplied with F-enriched drinking water (0.9 ppm F) during the years 1972-1984. Another 20% received F-containing mixed water (0.4-0.7 ppm F). During the first three decades of the study the level of caries prevalence was strictly correlated with the availability of an optimal caries preventive F concentration in the drinking water. Water fluoridation was followed by a decrease of caries, and interruptions in fluoridation were followed by increasing caries levels. A different caries trend was observed in the years from 1987 to 1995. There was a significant caries decrease down to the lowest DMFT (2.0) since 1959 in spite of the fact that only F-poor water was available over years in both towns. This improvement of oral health is explained by changes in caries-preventive and environmental conditions.

Adolescent↗
PubMed1996

Specific immune tolerance during pregnancy after renal transplantation.

Pregnancy is associated with specific immunological tolerance to fetal antigens suggesting that immunoregulatory processes during pregnancy can induce specific immunological unresponsiveness. We report a case of a female renal transplant recipient who stopped immunosuppressive therapy during first pregnancy. Despite histologically proven acute renal allograft rejection during the early course of transplantation, no immunological response was observed for 9 years after withdrawal of immunosuppression. Two further pregnancies within that time period did not evoke any renal complications, but were complicated by premature rupture of the amnion and by the development of preeclampsia. To our knowledge, there are no reports of such a long-term specific unresponsiveness to a renal allograft without immunosuppressive therapy. Natural and active immunoregulatory mechanism can be related for the development of specific immune tolerance to renal allograft in this case.

Adult↗
PubMed1996

Posttransplant lymphoproliferative disease after cardiac transplantation. Two unusual variants with predominantly plasmacytoid features.

Two patients who developed posttransplant lymphoproliferative disorder with plasmacytoid changes in the lymphocytes after heart transplant are described. The first case is one of multiple myeloma, and the second is a case of lymphoma with plasmacytoid features. The clinical course and the etiologic role of the immunosuppressive therapies that the patients received for heart transplantation are described. A review of posttransplant multiple myeloma and discussion of the etiology and prognosis of this entity are presented.

Heart Transplantation↗
PubMed1996

Identification of a novel RalGDS-related protein as a candidate effector for Ras and Rap1.

Although Ras and Rap1 share interaction with common candidate effector proteins, Rap1 lacks the transforming activity exhibited by Ras proteins. It has been speculated that Rap antagonizes Ras transformation through the formation of nonproductive complexes with critical Ras effector targets. To understand further the distinct biological functions of these two closely related proteins, we searched for Rap1b-binding proteins by yeast two-hybrid screening. We identified multiple clones that encode the COOH-terminal sequences of a protein that shares sequence identity with RalGDS and RGL, which we have designated RGL2. A 158-amino acid COOH-terminal fragment of RGL2 (RGL2 C-158) bound to Ras superfamily proteins which shared identical effector domain sequences with Rap1 (Ha-Ras, R-Ras, and TC21). RGL2 C-158 binding was impaired by effector domain mutations in Rap1b and Ha-Ras. Furthermore, RGL2 C-158 bound exclusively to the GTP-, but not the GDP-bound form of Ha-Ras. Finally, coexpression of RGL2 C-158 impaired oncogenic Ras activation of transcription from a Ras-responsive promoter element and focus-forming activity in NIH 3T3 cells. We conclude that RGL2 may be an effector for Ras and/or Rap proteins.

3T3 Cells↗
PubMed1996

Involvement of G alpha q/11 in the contractile signal transduction pathway of muscarinic M3 receptors in caecal smooth muscle.

The nature of the pertussis toxin-insensitive G-protein involved in muscarinic-mediated phosphoinositides breakdown and contraction of isolated smooth muscle cells from the circular layer of the rabbit caecum was investigated. Immunoblotting of membrane proteins using affinity purified antibodies directed against different G-protein alpha-subunits revealed the expression of G alpha q/11, G alpha 11 and G alpha 12 in these cells. The carbachol-mediated [3H]inositol phosphates accumulation in saponin-permeabilized cells was abolished by anti-G alpha q/11-antibodies whereas anti-G alpha i1,2-antibodies were ineffective. Moreover, the carbachol-induced contraction of permeabilized cells, as determined by videomicrocopic measurements, was reversed by anti-G alpha q/11-antibodies but not affected by anti-G alpha i1,2-antibodies. From these data, we conclude that carbachol stimulates phosphoinositides hydrolysis and cell contraction through activation of specific muscarinic M3 receptors coupled to the pertussis toxin-insensitive G alpha q/11-protein. This is the first demonstration of G alpha q/11 implication in the contractile signal transduction pathway of muscarinic M3 receptors in smooth muscle cells.

Animals↗
PubMed1996

Preeclampsia -- a state of sympathetic overactivity.

BACKGROUND: Preeclampsia is characterized by a marked increase in peripheral vascular resistance leading to an increase in blood pressure, but the triggering mechanisms are unclear. METHODS: To determine whether augmented sympathetic vasoconstrictor activity may be an important mechanism in mediating the increase in vasomotor tone, we measured postganglionic sympathetic-nerve activity in the blood vessels of skeletal muscle by means of intraneural microelectrodes in nine women with preeclampsia, eight normotensive pregnant women, six normotensive nonpregnant women, and seven nonpregnant women with hypertension, both at rest and during noninvasive cardiovascular-reflex testing (with the Valsalva maneuver and the cold pressor test). RESULTS: The mean (+/-SE) rate of sympathetic-nerve activity in the normotensive pregnant women (10+/-1 bursts per minute) was not significantly different from that in normotensive nonpregnant women (12+/-2 bursts per minute) or hypertensive nonpregnant women (15+/-3 bursts per minute). In contrast, the rate of sympathetic-nerve activity in the patients with preeclampsia (33+/-3 bursts per minute) was more than three times as high as that in the normotensive pregnant women (P<0.05) and more than twice as high as in the group of nonpregnant women with hypertension (P<0.05). Hemodynamic and sympathetic-nerve responses to both reflex tests did not differ significantly among the four groups. Six patients with preeclampsia were studied again after delivery; mean sympathetic-nerve activity at that time had decreased significantly from the value during pregnancy (from 36+/-4 to 13+/-2 bursts per minute, P<0.01), as had mean arterial pressure (from 118+/-3 to 96+/-1 mm Hg, P<0.01). CONCLUSIONS: Preeclampsia is a state of sympathetic overactivity, which reverts to normal after delivery. Our data indicate that the increases in peripheral vascular resistance and blood pressure that characterize this disorder are mediated, at least in part, by a substantial increase in sympathetic vasoconstrictor activity.

Action Potentials↗
PubMed1996

Cationic lipid mediated transfer of c-abl and bcr antisense oligonucleotides to immature normal myeloid cells: uptake, biological effects and modulation of gene expression.

Uptake and biochemical and biological effects of antisense oligodeoxynucleotides (ODN) specific for c-abl and bcr genes were studied in normal immature myeloid cells. CD34-positive cells were purified by positive and negative selection and cultured in liquid culture for 7 days. These cells were then incubated with ODNs, either alone or in combination with cationic lipids. The uptake of ODNs was enhanced by the use of cationic lipids. In addition, very low concentrations of ODNs in combination with cationic lipids were capable of specifically inhibiting the expression of the c-abl gene. In contrast, no effects were seen on the expression of bcr. However, despite the effective blocking of c-abl expression, no changes in cellular growth patterns were observed in liquid culture or in a colony-forming assay. We conclude tht the use of cationic lipids might enhance the gene-regulatory effects of ODNs by increasing their uptake into normal hematopoietic cells.

Antigens, CD34↗