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Biomedical subjects

M Schmidt

Publications and source records attributed to M Schmidt.

At least 271 records · Page 15Linked to original sources

Outcome variables in periodontal research: means and threshold-based site changes.

BACKGROUND: The exclusive use of mean measurements in periodontal research might at times be misleading, as changes in different sites in the same individual might nullify each other. The purpose of the present study was to compare disease progression and response to periodontal therapy using both individual site activity with thresholds and mean patient changes. METHODS: Seventy-nine (79) subjects with established periodontitis were monitored for 1 year (no treatment [NTx] group); 108 subjects who received scaling, root planing, and quarterly prophylaxis were observed in a similar time interval (treatment [Tx] group). Probing depth (PD), attachment level (AL) and alveolar crestal height (ACH) were measured at baseline and 1 year using pressure-sensitive probes and computer-assisted image analysis of radiographs. RESULTS: Mean reduction in PD (0.50 mm) was observed in the Tx group compared to a small increase (-0.04 mm) in the NTx group (P= 0.0001). Treatment resulted in mean AL gain (0.44 mm) compared to net AL loss (-0.21 mm) in the NTx group (P= 0.0001). Subjects in the Tx group had twice as many sites with AL gain (beyond the threshold) compared to NTx subjects (16.64+/-1.07% versus 8.11+/-0.68%) which was highly significant (P = 0.0001, Student t test). Similarly, although in the opposite direction, percentage of sites with AL loss beyond threshold was 6.21+/-0.47% (Tx group) and 14.02+/-1.15% (NTx group) which was also highly significant (P = 0.0001, Student t test). Change in ACH was minimal for the Tx group (-0.07+/-0.03 mm) while NTx subjects experienced greater bone loss throughout the year (-0.16+/-0.02 mm); percentage of sites with ACH loss was similar for both groups, while the Tx group had 3 times the number of sites with ACH gain (11.76% versus 3.42%), suggesting that the reduction in mean bone loss in the Tx group did not result from a reduction in losing sites, but rather from an increase in gaining sites. The use of both means and binary data seems to supplement the information regarding the nature and mechanism of disease progression and arrest. CONCLUSIONS: The characteristics of periodontal disease with its multifactorial patient, local, and site-related etiology support the use of both mean and site-based changes in clinical studies of periodontal disease and treatment.

Adult↗

Equilibrium-phase MR angiography of the aortoiliac and renal arteries using a blood pool contrast agent.

OBJECTIVE: The purpose of this study was to determine the diagnostic usefulness of a new blood pool contrast agent, NC100150, for assessing the aortoiliac and renal arteries. SUBJECTS AND METHODS: Twenty patients with hemodynamically significant stenosis (> or =50% of luminal diameter) of the iliac or renal arteries or an aortic aneurysm documented by digital subtraction angiography underwent MR angiography at 1.5 T after administration of NC100150. Three-dimensional MR angiographic data sets were collected ill the equilibrium phase. In a prospective analysis, each vascular segment (16 segments per arterial tree) was evaluated. RESULTS: All patients tolerated the NC100150 administration well. Mean contrast-to-noise ratios of the vascular data collected in the equilibrium phase of NC100150 was 3.3+/-15.9. Compared with digital subtraction angiography, the sensitivity and specificity of MR angiography for the renal arteries were 82% and 98%, respectively; for the common iliac arteries, 86% and 97%, respectively; for the external iliac arteries, 80% and 100%, respectively; and for the internal iliac arteries, 71% and 977, respectively. All 83 aneurysmal changes revealed by digital subtraction angiograpy of the aortoiliac arteries were well displayed on the MR angiographic data sets. CONCLUSION: Equilibrium-phase NC 00150-enhanced three-dimensional MR angiography shows high specificity when evaluating the abdominal and pelvic vascular systems, but the attendant venous overlap can limit the assessment of stenosis in renal and pelvic arterial segments.

Adult↗

E- and P-selectin expression in endometriotic tissues and the corresponding endometria.

Endometriosis is one of the most frequent diseases in gynecology. It is histologically defined as a non-malignant pathology in which endometrial-like tissue is found outside the uterus. The pathogenesis and mechanisms involved in the development of endometriosis-associated pain symptoms are still under investigation. A local peritoneal inflammation seems to play an important role in the origin of these symptoms. Selectins belong to a group of cell adhesion molecules that mediate the localization of circulating leukocytes on the endothelium at the sites of inflammation. The aim of this study was to investigate the expression of E- and P-selectins in endometriotic tissues and the corresponding endometria. Thirty endometriotic samples, 13 corresponding endometria and six endometria of patients without endometriosis were analyzed using an immunohistochemical technique. Just two endometriotic tissues expressed E-selectin, while five samples were positive for P-selectin. The selectin expression of the corresponding endometria was also very weak. No correlations between the revised American Fertility Society (rAFS) score or the hormonal situation of the patients at the time of biopsy and the selectin expression could be found. In conclusion, the selectin expression in endometriotic glands does not play an important role in the initiation of inflammatory processes caused by endometriosis. This inflammation must be considered as a secondary reaction after the implantation of the endometriotic glands, so that endometriotic tissues are not able to induce, by the expression of selectins, a direct inflammation.

Biopsy↗

Relationship between HPV infection of the cervix and blood serum levels of steroid hormones among pre- and postmenopausal women.

Human papillomaviruses (HPVs) are frequently present in anogenital lesions but little is known about their role in carcinogenesis. There are steroid hormone response elements in virus genomes that influence expression patterns of viral genes. Activity of the elements may contribute to development of neoplasia in case of hormone level anomalies. Our study was to determine whether the presence of HPV DNA in cervical smears correlates with abnormal levels, of steroid hormones in blood serum. One hundred women aged 40-62 participated in the tests and were divided into two groups: premenopausal and postmenopausal (45 and 55 individuals, respectively). Presence of HPV DNA in cervical smears was detected by PCR and Southern blot hybridisation. Progesterone and estradiol levels in blood serum were measured by radioimmunoassay. Our study showed a higher prevalence of HPV DNA in women with higher levels of progesterone in blood serum. A relationship between hormone level and HPV DNA prevalence should alert clinicians about using hormone contraceptives and hormone replacement therapy.

Adult↗

[Effect of iodine application during radioiodine therapy in patients with impending therapy failure].

AIM: We investigated whether additional application of "cold" iodine after therapy with radioiodine could result in a prolongation of the effective half life of iodine-131 and would thus lead to an increase of the effective thyroid radiation dose. METHODS: Time-activity-curves after therapy with radioiodine were analysed in 25 patients (16 women, 9 men). Nine patients suffered from autonomously functioning thyroid nodules, 5 from autonomous multinodular goiter and 11 from Graves' disease. These patients had an effective half life shorter than 4 days resulting in an undertreatment of > 20% with respect to the desired effective thyroid radiation dose. 2-4 days after therapy with radioiodine all patients received "cold" iodine for three days in a dose of 3 x 200 micrograms per day. RESULTS: In 14 of the 25 patients an increase of the effective half life was observed. Patients with an autonomously functioning thyroid nodule showed a mean increase of the effective thyroid radiation dose of 40 +/- 44 Gy, patients with toxic multinodular goiter of 29 +/- 30 Gy and patients with Graves' disease of 37 +/- 37 Gy. CONCLUSION: Additional application of "cold" iodine after therapy with radioiodine can prolong the effective half life in selected patients. We suspect a correlation with the thyroid iodine pool. This will be the basis for further investigations hopefully resulting in a better patient preselection to determine who might respond to this therapy.

Adult↗

New techniques in fast time-resolved structure determination.

New techniques in fast time-resolved X-ray crystallography provide a different approach to understanding the structural basis of protein function. Two biological systems have been studied as part of the refinement of these techniques, and have actually spurred new ideas in time-resolved structural studies. The dissociation of carbon monoxide from carbon-monoxy myoglobin has earlier been investigated over a time range spanning 18 orders of magnitude (femtoseconds to hours) using spectroscopic methods. Rapid time-resolved determination of the entire myoglobin structure made it possible to determine both the position of the CO after photodissociation and the entire globin structure, over a time range from nanoseconds to milliseconds, during which the heme and globin relax and the carbon monoxide rebinds. Photoactive yellow protein, a relative newcomer to biophysical research, has a fully-reversible photocycle containing several spectrally distinct intermediates. Identifying and solving the structures of each intermediate is the initial goal in time-resolved studies on this protein and will contribute to a greater understanding of the biological process of light driven signal transduction.

Animals↗

Differential expression of heat shock protein 70 (hsp70) in human monocytes rendered apoptotic by IL-4 or serum deprivation.

Apoptosis of monocytes is regulated by the balance between pro- and antiapoptotic triggers and pathways and may strongly influence inflammatory disorders. The major heat shock protein, hsp70, is an effective inhibitor of apoptosis in lymphocytic and monocytic tumor cell lines, but the implications in the regulation of apoptosis of freshly isolated human monocytes have not been elucidated. In this study, we examined whether two different triggers of monocyte apoptosis, serum deprivation and IL-4, respectively, altered hsp70 expression and whether expression levels correlated with monocyte survival. Monocyte apoptosis was determined quantitatively by flow cytometry detecting annexin V binding or nuclear stainability with propidium iodide (PI). Hsp70 expression was analyzed by semiquantitative RT-PCR and immunoblotting. Exposing monocytes to heat shock (47 degrees C, 20 min) induced a rapid and marked upregulation of hsp70 without evoking injury or apoptosis, suggesting that hsp70 conferred protection and survival. In accordance, when monocytes were rendered apoptotic by serum deprivation, a drastic downregulation of hsp70 occurred, which was accompanied by a reduced synthesis of the constitutive family member hsc70. However, induction of monocyte apoptosis by IL-4 increased hsp70 expression in a concentration and time-dependent fashion. A neutralizing antibody against IL-4 abolished hsp70 expression and apoptosis induction after IL-4 treatment and so excluded indirect effects. LPS rescued monocytes from apoptosis but did not alter hsp70 formation significantly. These findings suggest that, in monocytes, distinct apoptotic triggers induce different responses of hsp70 so that this molecule does not exert protection against cell death directly or in general.

Antibodies↗

Facilitating networks of information.

In this paper we describe an approach to respond to a request for information with the identification and location of the appropriate person as a source of information for answering the question. The expertise of a person is characterized using a weighted profile that has been derived from a series of documents describing the expert's activities. Having these profiles, requests for information can be matched with these profiles. The best matches correspond with the people that are experts for providing information on the request.

Abstracting and Indexing↗

Ovulation and embryonic developmental rate following hCG-stimulation in sows.

The hCG induced ovulation in sows was studied by use of ultrasonography, and an investigation of the development and diversity of the zygotes/embryos was performed at 24 h after ovulation. Crossbred sows (N = 48) were weaned (day 0) and checked for heat twice daily from day 3 onwards. From day 4, the ovaries were transrectally scanned twice daily. On day 4, the sows were given an injection of 750 iu hCG i.m. and inseminated 27 +/- 2 h (X +/- SD) and 38 +/- 1 h later. From 38 to 48 h after the hCG injection, the ovaries were scanned at 60 to 90 min intervals. At 24 h after ovulation the oviducts were surgically flushed in 18 sows. Out of the 48 sows, 34 showed heat at 12-36 h after the hCG-treatment and 14 showed heat before the hCG treatment. In the former group of sows, 20 (59%) ovulated within the interval of 38 to 48 h after the hCG treatment, and the follicular size immediately before ovulation was 7.8 +/- 0.6 mm. Among the sows which showed heat before hCG treatment only 7 (50%) ovulated within the above interval and the preovulatory follicle size was larger (8.3 +/- 0.5, p < 0.05) than in the former group of sows, which showed heat after the hCG treatment. The flushing of 18 sows yielded a total of 243 ova, 70 (29%) 1-cell stages, 160 (66%) 2-cell stages and 13 (5%) 4-cell stages. A pronounced difference in the degree of variation in embryonic development was seen between sows: 4 animals yielded 1- to 4-cell stages, one exclusively 2-cell stage. In conclusion, the control of ovulation in sows by hCG treatment will affect the follicular growth and the exact timing of ovulation can not always be relied on. It is strongly recommended to use ultrasonography to monitor the time of ovulation if this parameter is important. Ova recovered at 24 +/- 1 h after the median time of ovulation revealed a pronounced diversity (1- to 4-cell stage) within sows. No obvious relation with this embryonic diversity and the follicular size at ovulation was seen in these data.

Animals↗

Phospholipase D stimulation by receptor tyrosine kinases mediated by protein kinase C and a Ras/Ral signaling cascade.

Stimulation of phospholipase D (PLD) in HEK-293 cells expressing the M(3) muscarinic receptor by phorbol ester-activated protein kinase C (PKC) apparently involves Ral GTPases. We report here that PKC, but not muscarinic receptor-induced PLD stimulation in these cells, is strongly and specifically reduced by expression of dominant-negative RalA, G26A RalA, as well as dominant-negative Ras, S17N Ras. In contrast, overexpression of the Ras-activated Ral-specific guanine nucleotide exchange factor, Ral-GDS, specifically enhanced PKC-induced PLD stimulation. Moreover, recombinant Ral-GDS potentiated Ral-dependent PKC-induced PLD stimulation in membranes. Epidermal growth factor, platelet-derived growth factor, and insulin, ligands for receptor tyrosine kinases (RTKs) endogenously expressed in HEK-293 cells, apparently use the PKC- and Ras/Ral-dependent pathway for PLD stimulation. First, PLD stimulation by the RTK agonists was prevented by PKC inhibition and PKC down-regulation. Second, expression of dominant-negative RalA and Ras mutants strongly reduced RTK-induced PLD stimulation. Third, overexpression of Ral-GDS largely potentiated PLD stimulation by the RTK agonists. Finally, using the Ral binding domain of the Ral effector RLIP as an activation-specific probe for Ral proteins, it is demonstrated that endogenous RalA is activated by phorbol ester and RTK agonists. Taken together, strong evidence is provided that RTK-induced PLD stimulation in HEK-293 cells is mediated by PKC and a Ras/Ral signaling cascade.

Bacterial Proteins↗

Immunocytochemical localization of FLRFamide-, proctolin-, and CCAP-like peptides in the stomatogastric nervous system and neurohemal structures of the crayfish, Cherax destructor.

To compare the stomatogastric nervous system of the crayfish Cherax destructor with those of other decapod species, the distribution of FLRF (Phe-Leu-Arg-Phe) amide-, proctolin- and crustacean cardioactive peptide (CCAP)-like immunoreactivities was studied in the stomatogastric nervous system and in neurosecretory structures by using wholemount immunocytochemical techniques and confocal microscopy. In addition, the number of cells in the stomatogastric ganglion (19-24) and axon profiles in the stomatogastric nerve (157-165) were counted. FLRFamide-like immunoreactivity was present within numerous cell bodies and neuropil of the commissural ganglia, in the neuropil of the stomatogastric ganglion, and in one cell body of the esophageal ganglion. FLRFamide-like immunoreactivity was also found in two cell bodies at the junction of the stomatogastric nerve with the superior esophageal nerve and in two cell bodies in the inferior ventricular nerve. Proctolin-like immunoreactivity was present in numerous cell bodies and neuropil of the paired commissural ganglia and in the neuropil of the stomatogastric ganglion. CCAP-like immunoreactivity was found in the neuropil and in one to four cell bodies in the commissural ganglia. Both proctolin- and CCAP-immunoreactive varicosities occurred on the surface of the circumesophageal connectives and on the postesophageal commissure, indicating a neurohemal source within the stomatogastric nervous system, which was verified by electron microscopy. The pericardial organs showed FLRFamide-, proctolin-, and CCAP-like immunoreactivity. This staining pattern suggests that FLRFamide-like and proctolin-like peptides are used as neurohormones and as neuromodulators in the stomatogastric nervous system of the crayfish C. destructor, whereas CCAP-like peptides may only affect the stomatogastric ganglion as a neurohormone.

Animals↗

Role of sphingosine kinase in Ca(2+) signalling by epidermal growth factor receptor.

Contribution of sphingosine kinase (SPK)-catalyzed production of sphingosine-1-phosphate (SPP), in comparison to phospholipase C (PLC), to Ca(2+) signalling by epidermal growth factor (EGF) was studied in two HEK-293 cell clones (HEK2 and HEK3), expressing functional EGF receptors and exhibiting release of stored Ca(2+) by intracellular SPP. In HEK3 cells, EGF increased [Ca(2+)](i) and stimulated both, SPK and PLC. [Ca(2+)](i) increase, but not PLC stimulation, was strongly reduced by SPK inhibition. In HEK2 cells, EGF similarly stimulated PLC, but did not increase [Ca(2+)](i) or stimulate SPK, suggesting that intracellular SPP production plays a major role for Ca(2+) signalling by EGF in HEK-293 cells.

Calcium Signaling↗

The mycosubtilin synthetase of Bacillus subtilis ATCC6633: a multifunctional hybrid between a peptide synthetase, an amino transferase, and a fatty acid synthase.

Bacillus subtilis strain ATCC6633 has been identified as a producer of mycosubtilin, a potent antifungal peptide antibiotic. Mycosubtilin, which belongs to the iturin family of lipopeptide antibiotics, is characterized by a beta-amino fatty acid moiety linked to the circular heptapeptide Asn-Tyr-Asn-Gln-Pro-Ser-Asn, with the second, third, and sixth position present in the D-configuration. The gene cluster from B. subtilis ATCC6633 specifying the biosynthesis of mycosubtilin was identified. The putative operon spans 38 kb and consists of four ORFs, designated fenF, mycA, mycB, and mycC, with strong homologies to the family of peptide synthetases. Biochemical characterization showed that MycB specifically adenylates tyrosine, as expected for mycosubtilin synthetase, and insertional mutagenesis of the operon resulted in a mycosubtilin-negative phenotype. The mycosubtilin synthetase reveals features unique for peptide synthetases as well as for fatty acid synthases: (i) The mycosubtilin synthase subunit A (MycA) combines functional domains derived from peptide synthetases, amino transferases, and fatty acid synthases. MycA represents the first example of a natural hybrid between these enzyme families. (ii) The organization of the synthetase subunits deviates from that commonly found in peptide synthetases. On the basis of the described characteristics of the mycosubtilin synthetase, we present a model for the biosynthesis of iturin lipopeptide antibiotics. Comparison of the sequences flanking the mycosubtilin operon of B. subtilis ATCC6633, with the complete genome sequence of B. subtilis strain 168 indicates that the fengycin and mycosubtilin lipopeptide synthetase operons are exchanged between the two B. subtilis strains.

Adenosine Monophosphate↗

[Clinical value of magnetic resonance tomography in imaging coronary stenoses. A comparison with coronary angiography and myocardial scintigraphy].

BACKGROUND AND OBJECTIVE: The development of ultra-rapid gradient-echo sequence magnetic resonance imaging (MRI) makes it possible to visualize coronary arteries. But the clinical value of coronary artery MRI (MRCA) still needs to be established. It was the aim of this study to determine whether MRCA can demonstrate proximal parts of the coronary arteries and visualize haemodynamically relevant stenoses. PATIENTS AND METHODS: MRCA was performed, using segmented 2D sequences and a navigator pulse, in 29 patients (22 men, seven women, mean age 60 +/- 10 years) in whom coronary heart disease (CHD) was suspected or who, with proven CHD (> or = 50% stenosis) further treatment was to be established. Exercise myocardial scintigraphy with single proton emission tomography (SPECT) was additionally performed in 20 of the patients. RESULTS: Seven of 87 coronary arteries (8%) could not be demonstrated because the patients' claustrophobia necessitated premature termination of the investigation: these vessels were excluded from the final analysis. The mean length of the visualized coronary arteries was 12 +/- 4 mm for the main stem (LM), 36 +/- 14 mm for the left interventricular branch (LAD), 18 +/- 12 mm for the circumflex branch (CX) and 67 +/- 23 mm for the right coronary artery (RCA). Of 37 stenoses demonstrated by coronary angiography 29 were also visualized by MRCA: 13 of 18 LAD stenoses, two of three CX stenoses and 14 of 16 RCA stenoses. Mean sensitivity of MRCA was 78%, mean specificity 86%. In patients who had undergone exercise SPECT, coronary angiography demonstrated 26 stenoses, of which 16 (six LAD, two CX and eight RCA stenoses) were haemodynamically significant. Of these 16 stenoses MRCA demonstrated 13, but three stenoses (one RCA and two LAD stenoses) were not visualized, because the stenoses were distal to the demonstrated segments. CONCLUSION: MRCA can visualize moderately severe stenoses, especially of the proximal coronary arterial segments. This method represents an new approach to noninvasive diagnosis of CHD, but additional technical improvements will have to be made.

Adult↗

Glucocorticoids induce apoptosis in human monocytes: potential role of IL-1 beta.

Glucocorticoids (GC) are potent anti-inflammatory and immunosuppressive agents that act on a variety of immune cells, including monocytes and macrophages. However, the exact cellular mechanisms underlying this anti-inflammatory capacity are still unknown. In our study, we determined the induction of apoptosis by GC in human monocytes. Peripheral blood monocytes were isolated by density centrifugation methods with a purity of >90% and were cultured in RPMI 1640 medium. Monocyte apoptosis was determined by four independent methods, including annexin-V staining, TUNEL, DNA-laddering, and typical morphology by means of transmission electron microscopy. TNF-alpha and IL-1beta were measured by ELISA. GC receptor was blocked with mifepristone. Caspase 3 was inhibited with caspase-3 inhibitor (DEVD-CHO). Stimulation with different GC at therapeutic concentrations resulted in monocyte apoptosis in a time- and dose-dependent manner. Necrosis was excluded by propidium iodide staining. Proinflammatory cytokines such as IL-1beta and TNF-alpha were down-regulated by GC treatment. Continuous treatment of monocytes with IL-1beta, but not with TNF-alpha, could almost completely prevent GC-induced cell death. The addition of mifepristone or caspase-3 inhibitor could partially abrogate GC-induced apoptosis as well as GC-induced inhibition of IL-1beta. This is the first study to demonstrate induction of apoptosis by GC in human monocytes. GC-induced monocyte apoptosis may be partially mediated through effects on IL-1beta production. It is conceivable that GC exert their anti-inflammatory capacity in various diseases, at least in part, by the induction of apoptosis in monocytes.

Apoptosis↗

Mutational analysis of subunit i beta2 (MECL-1) demonstrates conservation of cleavage specificity between yeast and mammalian proteasomes.

Proteasomes are the major protein-degrading complexes in the cytosol and regulate many cellular processes. To examine the functional importance of the MC14/MECL-1 proteasome active site subunits, cell lines expressing a catalytically inactive form of MECL-1 were established. Whereas mutant MECL-1 was readily incorporated into cytosolic proteasomes, replacing the constitutive MC14 subunit, removal of the prosequence was incomplete indicating that its processing required autocatalytic cleavage. Functional analyses showed that the absence of the MC14/MECL-1 active sites abrogated proteasomal trypsin-like activity, but did not affect other catalytic activities. Our data demonstrate a conservation of cleavage specificity between mammalian and yeast proteasomes.

Amino Acid Sequence↗