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T Schroeder

Publications and source records attributed to T Schroeder.

At least 73 records · Page 4Linked to original sources
PubMed2000

Role of third intracellular loop of galanin receptor type 1 in signal transduction.

To determine the domains essential for G-protein coupling of the human galanin receptor type 1 (GalR1), we have used both GalR1 mutants and synthetic receptor-derived peptides in(125)I-galanin and [(35)S]-GTPgammaS binding studies. Replacement of potential phosphorylation sites by Leu in the third intracellular loop (IC3) of GalR1 did not affect K(D)values for the receptor. Peptides derived form the IC3 loop, and especially the N-terminal part of it were able to increase the rate of [(35)S]-GTPgammaS binding to the trimeric Gialpha1beta1gamma2, but not to Gsalphabeta1gamma2, whereas the peptides corresponding to the IC1 and IC2 loops had no such effect. IC3 loop peptides also inhibited the binding of(125)I-galanin to GalR1 in membranes from Rin m5F cells. Our results suggest that the IC3 loop of GalR1, especially its N-terminal part, defines the coupling of the receptor to the Gialpha1beta1gamma2 protein and consequently, to the signal transduction cascade.

Amino Acid Sequence↗
PubMed2000

Generation of functionally mature dendritic cells from the multipotential stem cell line FDCP-mix.

Dendritic cells (DCs) are crucial components of the immune system because of their unique ability as antigen-presenting cells for the initiation of a primary immune response. DCs, macrophages (Ms) and granulocytes (Gs) are believed to originate from a common myeloid progenitor cell. However, little is known about the molecular mechanisms leading to DC sublineage commitment. To establish a cell system that allows the molecular and biochemical analysis of DC differentiation and activation, we used the murine non-leukaemic, multipotential stem cell line FDCP-mix. FDCP-mix cells were cultured in various amounts of GM-colony stimulating factor (CSF) and interleukin (IL)-4 for up to 16 d and analysed for morphology, expression of CD34, c-kit, Gr-1, Mac-1, CD40, MHC-I, MHC-II and co-stimulatory molecules (CD80, CD86) using flow cytometry, and for their capacity to present foreign antigen to autologous T cells. Up to d 7, the majority of FDCP-mix cells consisted of cells differentiating along the G and M lineage. Thereafter, the number of dendritic cells increased until d 13. Differentiation along the DC lineage vs. the G and M lineage was favoured when FDCP-mix cells were cultured in high concentration GM-CSF (500 U/ml) throughout the culture and IL-4 from d 9 onwards. The dendritic cells generated from FDCP-mix cells were large, non-adherent cells with veiled processes and expressed MHC II, CD40, CD80 and CD86. After pulsing with a foreign antigen (keyhole limpet haemocyanin), FDCP-mix-derived dendritic cells stimulated [(3)H]-thymidine incorporation of naive T-cells in an autologous mixed lymphocyte reaction (MLR). Our results show that functionally mature dendritic cells are generated from the multipotential stem cell line FDCP-mix. This cell line thus provides the unique possibility of establishing multipotential transgenic cell lines capable of differentiation along the DC lineage. The experimental system described here should prove a valuable tool for studying DC differentiation and function.

Animals↗
PubMed1999

Effects of chirality at Tyr13 on the structure-activity relationships of omega-conotoxins from Conus magus.

The effects of chirality inversions of Tyr13 on the structure-activity relationships of omega-conotoxins MVIIA and MVIIC were examined using a combination of 2D 1H NMR spectroscopy and radioligand binding studies specific for N-type ([125I]GVIA) and P/Q-type ([125I]MVIIC) voltage-sensitive calcium channels (VSCCs). A comparison of the Halpha secondary shifts suggests that the structural scaffolds of MVIIA and MVIIC are little altered by the L- to D- inversion of Tyr13; however, the conformations of several residues in loop 2 (residues 9-14) are significantly altered. The experimentally determined 3D structure of [D-Y13]MVIIA indicates that the positions of key residues in this loop which are involved in the binding of MVIIA to the N-type VSCC (Tyr13, Arg10, and Leu11) are so changed as to render the peptide unrecognizable by its cognate ion channel. The large reduction in potency observed for MVIIA and MVIIC at both N-type and P/Q-type VSCCs is likely to stem from the change in conformation and orientation of loop 2.

Amino Acid Sequence↗
PubMed1999

Heparan sulfate proteoglycan expression is induced during early erythroid differentiation of multipotent hematopoietic stem cells.

Heparan sulfate (HS) proteoglycans of bone marrow (BM) stromal cells and their extracellular matrix are important components of the microenvironment of hematopoietic tissues and are involved in the interaction of hematopoietic stem and stromal cells. Although previous studies have emphasized the role of HS proteoglycan synthesis by BM stromal cells, we have recently shown that the human hematopoietic progenitor cell line TF-1 also expressed an HS proteoglycan. Immunochemical, reverse transcriptase-polymerase chain reaction (RT-PCR), and Northern blot analysis of this HS proteoglycan showed that it was not related to the syndecan family of HS proteoglycans or to glypican. To answer the question of whether the expression of HS proteoglycans is associated with the differentiation state of hematopoietic progenitor cells, we have analyzed the proteoglycan synthesis of several murine and human hematopoietic progenitor cell lines. Proteoglycans were isolated from metabolically labeled cells and purified by several chromatographic steps. Isolation and characterization of proteoglycans from the cell lines HEL and ELM-D, which like TF-1 cells have an immature erythroid phenotype, showed that these cells synthesize the same HS proteoglycan, previously detected in TF-1 cells, as a major proteoglycan. In contrast, cell lines of the myeloid lineage, like the myeloblastic/promyelocytic cell lines B1 and B2, do not express HS proteoglycans. Taken together, our data strongly suggest that expression of this HS proteoglycan in hematopoietic progenitor cell lines is associated with the erythroid lineage. To prove this association we have analyzed the proteoglycan expression in the nonleukemic multipotent stem cell line FDCP-Mix-A4 after induction of erythroid or granulocytic differentiation. Our data show that HS proteoglycan expression is induced during early erythroid differentiation of multipotent hematopoietic stem cells. In contrast, during granulocytic differentiation, no expression of HS proteoglycans was observed.

Cell Differentiation↗
PubMed1998

Temperature adaptation of house keeping and heat shock gene expression in Neurospora crassa.

Adaptation of house keeping and heat shock gene expression was determined in Neurospora crassa during continuous exposure to different temperatures. Steady-state values of total protein synthesis differed little after incubation for 24 h at temperatures between 15 and 42 degreesC. Adaptation kinetics at 42 degreesC showed an initial, transient inhibition of total protein synthesis. Similar kinetics were observed with actin synthesis and tubulin mRNA. A priming 1-h heat shock of 42 degreesC 2 h prior to a second continuous exposure to 42 degreesC abolished the inhibitory effect of the second treatment and resulted in "acquired translational tolerance." Steady-state values of HSP70 synthesis rates revealed increasing levels with increasing temperatures after incubation for 24 h at different temperatures. Adaptation kinetics of the synthesis rates of different HSPs in vivo revealed maximal rates after 2 h and then a decrease to the elevated steady-state levels. The total amount of the major constitutive and inducible HSP70 isoform as determined by Western blots reached a maximum 2 h after the beginning of 42 degreesC exposure and only a slight decrease (25%) of the maximal value after 24 h. The inducible isoform of HSP70, in contrast, reached a maximum after 4-8 h and then decreased strongly after 24 h. HSP mRNAs reached maximal amounts 45-60 min after the beginning of 42 degreesC exposure and then declined after 8 h as determined by in vitro translation. Northern blots revealed maximal mRNA amounts of the inducible HSP70 after 30 min and zero amounts after 4 h exposure to 42 degreesC. After a shift to 42 degreesC HSP70 isoforms were immediately translocated into the nucleus and reshuttled into the cytoplasm during the following 6 h. The nuclear content of HSP70 remained elevated during the adapted steady state at 24 h. It is concluded that the adapted state after 24 h is based on enhanced amounts of constitutive isoforms in the cytoplasm and in the nucleus, whereas the inducible isoforms of HSP70 show faster adaptation kinetics.

Adaptation, Physiological↗
PubMed1997

Preoperative ultrasound mapping of the saphenous vein: prognostic value on early post operative results, a prospective study.

A prospective series of 92 patients had their greater saphenous vein assessed with duplex ultrasound scanning prior to planned infrainguinal bypass procedures. Sixteen (17%) bypass procedures thrombosed within the first week postoperatively. A naturally occurring optimal vein diameter was discovered: 3.5-4.2 mm at mid-thigh level and 0-1.5 mm less at mid-calf level. It was significantly correlated with higher one week patency: thrombosis occurred in 11% in veins with this optimal diameter combination and in 19% in all other combination (P < 0.05). These results confirm and expand a retrospective study.

Aged↗
PubMed1996

Increased expression of proliferating cell nuclear antigen in liver allograft rejection.

Detection of proliferating cell nuclear antigen is useful for the study of proliferative activity of neoplastic and non-neoplastic lymphoid, parenchymal, and mesenchymal cells. Allograft rejection is associated with the recruitment of circulating cells and their proliferation in the graft. The intrahepatic expression of proliferating cell nuclear antigen on paraffin-embedded liver biopsy specimens (n = 110 from 32 patients) was examined by an avidin-biotin peroxidase method using a monoclonal antibody to proliferating cell nuclear antigen. The percentage of positive nuclei was determined in hepatocytes, biliary epithelium, and lymphocytes. There were four histologic groups: 1, moderate-to-severe rejection (n = 19); 2, mild rejection (n = 28); 3, nonspecific inflammation (n = 45); and 4, donor livers (n = 18). The percentage of positive nuclei was higher in group 1 compared to group 2 (hepatocytes p = 0.01; biliary epithelium p = 0.0007; lymphocytes p = 0.0001), to group 3 (hepatocytes p = 0.0002; biliary epithelium p = 0.0001; lymphocytes p = 0.0001), and to group 4 (for all three locations p < 0.0001). When group 2 was compared to group 3 the results were significant for biliary epithelium (p = 0.0001) and lymphocytes (p = 0.0001), but not for hepatocytes (p = 0.07). We conclude that proliferating cell nuclear antigen expression, especially in lymphocytes, correlates with the severity of histologic rejection. Proliferating cell nuclear antigen expression may be useful in predicting the progression and response to different antirejection therapies.

Analysis of Variance↗
PubMed1996

Are self-expanding stents superior to balloon-expanded in dilating aortas? An experimental study in pigs.

OBJECTIVE: To study the stent/vessel interaction and distensibility following the natural increase in vascular diameter using self-expanding and balloon-expanded stents. DESIGN: Open experimental study. SETTING: Animal laboratory, university hospital. MATERIALS AND METHODS: Eight Palmaz (P) and eight Gianturco (G) stents were transluminally placed in the infrarenal aortas of 16 pigs. Pulsatile diameter changes above, at and below the stents were non-invasively monitored with an ultrasound phase-locked echo-tracking system before and immediately after stenting and at 4 and 18 weeks. Blood pressure was registered intra-arterially and stiffness (beta) was calculated. Intravascular ultrasound (IVUS) was performed at 18 weeks. RESULTS: Median weight increased from 20 kg (19-26) to 93 kg (62-130). Diameter of the aorta increased 60%. In group P no pulsatile diameter change could be measured at the stent (beta = infinity). In group G stenting increased stiffness from beta 20.7 (9.2) to 43.2 (8.0) (p < 0.05). After 18 weeks stiffness returned to beta 20.1 (12.4). Expanded, median diameter of the P stents was 7.4 (0.8) mm, not increasing after 18 weeks. Initial diameter of the G stents was 7.8 (1.0) mm, increasing 56% to 12.2 (2.3) mm (p < 0.05). IVUS revealed the G stents to be well attached to the vascular wall, but five P stents were detached within half of the circumference. CONCLUSION: Self-expanding stents follow the pulsatile diameter change of the vessel wall, not adversely affecting distensibility after 18 weeks. They show good attachment despite 56% dilation. In contrast, the balloon-expanded stents do not show pulsatile movement and may detach during vessel diameter increase. This may be of importance when choosing stents for endovascular treatment of abdominal aortic aneurysms.

Animals↗
PubMed1996

Correction of blood pH attenuates changes in hemodynamics and organ blood flow during permissive hypercapnia.

OBJECTIVES: To determine whether changes in cardiac output, regional blood flow, and intracranial pressure during permissive hypercapnia are blood pH-dependent and can be attenuated by correction of intravascular acidemia. DESIGN: Prospective, controlled study. SETTING: Research laboratory. SUBJECTS: Female Marino ewes. INTERVENTIONS: Animals were instrumented with a pulmonary artery catheter, femoral arterial and venous catheters, a catheter in the third cerebral ventricle, and ultrasonic flow probes on the left carotid, superior mesenteric, and left renal arteries 1 wk before experimentation. At initiation of the protocol, ewes underwent endotracheal intubation and mechanical ventilation under general anesthesia. Minute ventilation was reduced to induce hypercapnia with a target PaCO2 of 80 torr (10.7 kPa). In the pH-uncorrected group (n = 6), arterial blood pH was allowed to decreased without treatment. In the pH-corrected group (n = 5), 14.4 mEq/kg of sodium bicarbonate was given intravenously as a bolus to correct arterial blood pH toward a target arterial pH of 7.40 (dose calculated by the Henderson-Hasselbalch equation). MEASUREMENTS AND MAIN RESULTS: Arterial blood pH, PCO2, cardiac output, intracranial pressure, and carotid, superior mesenteric, and renal artery blood flow rates were measured at normocapnic baseline and at every hour during hypercapnia for 6 hrs. In the pH-uncorrected group, arterial blood pH decreased from 7.41 +/- 0.03 at normocapnia to 7.14 +/- 0.01 (p < .01 vs. normocapnia) as blood PCO2 increased to 81.2 +/- 1.8 torr (10.8 +/- 0.2 kPa). In the pH-corrected group, arterial blood pH was 7.42 +/- 0.02 at normocapnia and was maintained at 7.37 +/- 0.01 while PaCO2 was increased to 80.3 +/- 0.9 torr (10.7 +/- 0.1 kPa). Significant increases in cardiac output occurred with the initiation of hypercapnia for both groups (pH-uncorrected group: 4.3 +/- 0.6 L/min at normocapnia vs. 6.8 +/- 1.0 L/min at 1 hr [p < .05]; pH-corrected group: 4.1 +/- 0.4 at normocapnia vs. 5.7 +/- 0.4 L/min at 1 hr [p < .05]). However, this increase was sustained only in the uncorrected group. Changes in carotid and mesenteric artery blood flow rates, as a percent of baseline values, showed sustained significant increases in the pH-uncorrected groups (p < .05) and only transient (carotid at 1 hr) or no (superior mesenteric) significant change in the pH-corrected groups. Conversely, significant increases in renal artery blood flow were seen only in the pH-uncorrected group during the last 2 hrs of the experiment (p < .05). Organ blood flow, as a percent of cardiac output, did not change significantly in either group. Intracranial pressure increased significantly in the pH-uncorrected group (9.0 +/- 1.5 mm Hg at normocapnia vs. 26.8 +/- 5.1 at 1 hr, p < .05), and remained increased, while showing no significant change in the pH-corrected group (8.5 +/- 1.6 mm Hg at normocapnia to 7.7 +/- 4.2 at 1 hr). CONCLUSIONS: Acute hypercapnia, induced within 1 hr, is associated with significant increases in cardiac output, organ blood flow, and intracranial pressure. These changes can be significantly attenuated by correction of blood pH with the administration of sodium bicarbonate, without adverse effects on hemodynamics.

Acute Disease↗
PubMed1996

Serial monitoring of soluble interleukin-2 receptor as a rapid marker of cytomegalovirus infection and response to antiviral therapy.

Serial sIL-2R serum levels were evaluated as an indicator of cytomegalovirus infection and response to antiviral therapy. All cases of post-transplant CMV infection or disease were studied over a 2.5-year period with serial sIL-2R serum levels monitored daily post-transplant until discharge, during each inpatient admission and with each outpatient laboratory analysis. Mean sIL-2 levels +/- S.E.M. rose from a baseline level of 3662 +/- 321 U/ml to 11657 +/- 3311 U/ml at the time of diagnosis. Serum sIL-2R concentrations were significantly elevated from baseline as early as 14 days prior to diagnosis of CMV. Mean peak sIL-2R levels occurred an average of 4 days after the initiation of ganciclovir therapy and remained significantly elevated for an average of 20 days of treatment. Serum sIL-2R levels in patients with resolved CMV returned to within 20% of baseline after 20 days of therapy. These data support the idea that serial monitoring of sIL-2R serum levels may be useful adjunctively in the diagnosis of CMV as well as determining the response to and duration of antiviral therapy.

Adult↗
PubMed1995

Paradoxical puborectalis contraction in patients after pelvic pouch construction.

UNLABELLED: Normal defecation is associated with relaxation of sphincters during the evacuation process. However, obstructive defecation is sometimes seen clinically manifested by abnormal contraction of the puborectalis during defecation rather than relaxing. This condition has not previously been described after pelvic pouch construction. PURPOSE: This study was done to evaluate patients for defecation difficulties caused by paradoxical puborectalis contraction after pelvic pouch procedures. METHODS: Prospectively, patients with defecation difficulties were questioned. They then underwent electromyography if they met particular criteria. Biofeedback was offered to all patients demonstrating paradox on electromyography. Follow-up was by clinic visits and interviews. RESULTS: After pelvic pouch construction, 13 patients were found to have paradoxical puborectalis contraction. Twelve of 13 patients elected to have biofeedback therapy. Eleven of these 12 were available for follow-up an average of eight (1-15) months after biofeedback. Nine improved, and two had no change in their defecation difficulty. Of the initial 13, 10 had an event, either pouchitis or abdominal trauma, directly before their defecation problems. CONCLUSION: Paradoxical puborectalis contraction can occur in patients after pelvic pouch surgery. It should be suspected in patients with defecation difficulties in the absence of an anatomic abnormality. Biofeedback is effective treatment.

Biofeedback, Psychology↗
PubMed1993

Predicting the functional result of anastomoses to the anus: the paradox of preoperative anal resting pressure.

UNLABELLED: This article examines the effect of ileal pouch-anal (n = 134) and coloanal (n = 16) anastomoses on resting anal canal pressures in 150 patients. METHODS: Patients underwent anal manometry before ileal pouch-anal anastomosis (IPAA) and coloanal anastomosis (CAA) and again six weeks after ileostomy closure following these procedures. A water-perfused catheter system with four radial ports was used for manometry, pressures being recorded during both station and continuous pull through. RESULTS: Patients with IPAA were younger than those with CAA (34 years vs. 50 years) and had a different ratio of hand-to-stapled anastomosis (1:2.6 vs. 1.3:1). All CAA patients had had rectal cancer while IPAA patients suffered mainly from ulcerative colitis (n = 114) or familial polyposis (n = 10). The mean preoperative resting pressure for all patients was 79 mmHg (75-87, 95 percent confidence limit) and the mean fall in this pressure after surgery was 25 mmHg (-21 to -29, 95 percent confidence limit). There was no difference in preoperative pressure or fall between handsewn and stapled anastomoses, or between IPAA and CAA. CONCLUSION: There was a significant relationship between preoperative pressure and change in pressure that held true for all subgroups (change = -0.7 x preoperative pressure + 31, r = 0.69). Analysis of the functional results confirmed that patients with high preoperative pressure are at risk for severe falls after surgery and are not guaranteed a good result. Conversely, patients with low preoperative pressures may actually have an increase with surgery and are not always incontinent. Patients with low preoperative anal resting pressures should not be denied anastomosis to the anus if they are continent.

Adolescent↗
PubMed1993

Endoluminal ultrasound is preferable to electromyography in mapping anal sphincteric defects.

Assessment of complex sphincteric defects in patients with fecal incontinence by digital rectal examination and intraoperative dissection can be difficult in the presence of excessive scarring. Adjunctive investigation such as endoluminal ultrasound (ELUS) and needle electromyography (EMG) may provide objective evidence of the nature and extent of the sphincteric defects. In a series of 11 patients, ELUS of the anal canal with a 10-MHz transducer (focal zone of 1-4 cm) accurately detected defects in the external anal sphincter (EAS) in seven of seven patients, defects in the internal anal sphincter (IAS) in eight of eight patients, and integrity of both sphincters in two patients. These findings were confirmed by needle EMG of the EAS alone in five patients, by operative findings at a perineal sphincteroplasty operation in six patients, and by both in two patients. ELUS was associated with less pain than was needle EMG (pain score 4 vs. 10, 10 being most painful) and provided high-resolution radial images of both the EAS and the IAS. Thus, ELUS seems preferable to EMG in mapping anal sphincteric defects and can be a useful anatomic adjunct to physiologic studies of anorectal function in patients with fecal incontinence.

Adult↗
PubMed1993

Analysis of the neutralizing antibody response to the measles virus using synthetic peptides of the haemagglutinin protein.

Infection or immunization with measles virus induces a protective immune reaction including neutralizing antibodies against the haemagglutinin and fusion protein. The reactivity of the polyclonal IgG response of sera obtained from late convalescent donors was studied, using overlapping 15mer peptides covering the complete sequence of the measles virus haemagglutinin. Most sera reacted with a similar set of peptides generating a characteristic binding pattern. The reactive peptides correspond to a region mediating cell hemolysis (aa310-325), to regions which serve as targets to neutralizing antibodies and to a putative transmembrane region (aa35-58). The latter region contains also a human T-cell epitope providing evidence of a non-random association of T- and B-cell epitopes. We also immunized different strains of mice and rabbits with measles virus. In contrast to the human sera, animal sera with strong neutralizing activities did not react with any of the H-protein peptides. The mostly weak reactivities with the linear sequences contrast with the strong neutralizing activities of the human or animal antibodies, suggesting that these primarily recognize the fusion protein or conformational epitopes of the haemagglutinin protein.

Adult↗
PubMed1993

Intra-arterial papaverine and leg vascular resistance during in situ bypass surgery with high or low epidural anaesthesia.

In situ saphenous vein arterial bypass flow was studied in 16 patients with respect to level of epidural anaesthesia. Arterial pressure and electromagnetic flow were used to evaluate arterial tone by intra-arterial (i.a.) papaverine. Eight patients had a low epidural block (< or = Th. 10) and eight patients were operated during high epidural anaesthesia (> Th. 10). Flow increased and arterial pressure decreased after i.a. papaverine in all patients. When compared with patients operated during high epidural anaesthesia, flow increase and decrease in vascular resistance took place in patients operated during low epidural anaesthesia (P < 0.02). Increase in arterial flow after i.a. papaverine was not significantly different in patients operated in low epidural and general anaesthesia (n = 8). In eight patients with insulin-dependent diabetes mellitus who had low epidural anaesthesia, the increase in flow after i.a. papaverine was not significantly different to that noted during high epidural anaesthesia. The results indicate that the level of analgesia influences graft flow after i.a. papaverine, probably reflecting differences in the effect of epidural anaesthesia on sympathetic tone to the leg.

Adult↗
PubMed1992

Noncytotoxic drug therapy for intra-abdominal desmoid tumor in patients with familial adenomatous polyposis.

Forty of 416 patients with familial adenomatous polyposis were noted to have intra-abdominal desmoid tumors, and a subgroup of 16 were treated with noncytotoxic drug therapy. Drugs used were sulindac (14 patients), sulindac plus tamoxifen (3 patients), indomethacin (4 patients), tamoxifen (4 patients), progesterone (DEPO-PROVERA; Upjohn Co., Kalamazoo, MI) (2 patients), and testolactone (1 patient). Therapy with these drugs for continuous periods of six months or more resulted in three complete and seven partial remissions. When treated patients were compared with untreated patients (n = 12), there were significant benefits for the treated group, both in reduction of desmoid size and in improvement of symptoms, despite the inherent selection bias against this. Sulindac was the only drug used in enough patients to permit independent evaluation of its effect, with one complete and seven partial reductions of tumor size. Some patients had a delayed response to sulindac, with tumor shrinkage occurring after an initial period of tumor enlargement. When using sulindac for the treatment of desmoid tumors, this phenomenon should be considered.

Abdominal Neoplasms↗