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Biomedical subjects

T Moritz

Publications and source records attributed to T Moritz.

At least 91 records · Page 5Linked to original sources

Quantitation of Gibberellins A(1), A(3), A(4), A(9) and a Putative A(9)-Conjugate in Grafts of Sitka Spruce (Picea sitchensis) during the Period of Shoot Elongation.

The levels of endogenous gibberellin A(1) (GA(1)), GA(3), GA(4), GA(9), and a cellulase hydrolyzable GA(9) conjugate in needles and shoot stems of mature grafts of Sitka spruce (Picea sitchensis [Bong.] Carr.) grown under environmental conditions that were either inductive, hot, and dry, or noninductive, cool, and wet, for flowering, were estimated by combined gas chromatography-mass spectrometry selected ion monitoring using deuterated [(2)H(2)]GA(1), GA(3), GA(4), and GA(9) as internal standards. The samples were taken when the shoots had elongated about 30, 70, and 95% of the final shoot length and 17 days after elongation had terminated. The concentration of putative GA(9)-conjugate, estimated by GCSIM of GA(9) after cellulase hydrolysis of the highly water soluble fraction, was 33 nanograms per gram fresh weight in the needles of both heat and drought- and cool and wet-treated plants sampled just after bud burst. The concentration gradually decreased to a final value of 13 nanograms per gram fresh weight in the heat and drought-treated grafts and 6 nanograms per gram fresh weight in the cool and wet-treated grafts. The stems contained no detectable putative GA(9) conjugate. Free GA(9) was highest in heat and drought-treated material. For plants subjected to this treatment, GA(9) increased from 22 to 32 nanograms per gram fresh weight in needles and from 1 to 22 nanograms per gram fresh weight in stems during the rapid stem elongation phase. By day 17, after cessation of shoot elongation, GA(9) had decreased to 12 nanograms per gram fresh weight in needles and 9 nanograms per gram fresh weight in the shoot stems. The cool and wet-treated material also showed an increase in GA(9) concentration during shoot elongation. However, the concentration was not as high and was also delayed compared with heat and drought-treated material. By day 17, after cessation of shoot elongation, GA(9) concentration was 9 nanograms per gram fresh weight in needles and 5 nanograms per gram fresh weight in stems for cool and wet treatment plants. The concentration of GA(4) was very low in tissue from both treatments. Fluctuation in concentration of the more polar gibberellins, GA(1) and GA(3), showed the same pattern as fluctuations in the content of GA(9). However, the heat and drought-treated material had lower amounts of GA(1) and GA(3) during the later phases of shoot elongation, than the cool and wet-treated material. These results imply differential metabolism between clones treated with conditions inductive and noninductive for flowering. Higher concentrations of putative GA(9) conjugate and free GA(9) in the hot and dry treatment indicate a higher capacity of synthesizing, for flowering, the physiologically important GA(4) in the heat and drought-treated material. This synthesis does not, however, result in a buildup of the GA(4) pool, probably because of a high turnover rate of GA(4). The cool and wet-treated material had higher amounts of GA(1) and GA(3), indicating that the differentiation was preferentially directed toward vegetative growth.

Journal Article↗

Internal mammary artery and saphenous vein graft patency. Effects of aspirin.

As part of two Department of Veterans Affairs Cooperative Trials, we obtained angiographic patency data for internal mammary artery (IMA) and saphenous vein grafts to the left anterior descending (LAD) coronary artery at 1 year after coronary artery bypass surgery. Patients received either aspirin 325 mg q.d., aspirin 325 mg t.i.d., aspirin 325 mg and dipyridamole 75 mg t.i.d., or placebo. Aspirin was initiated either 12 hours before or 6 hours after operation. Patients were stratified preoperatively for extent of disease and randomized to the therapies outlined above. There was no randomization to IMA versus saphenous vein grafts to the LAD. When the patients taking placebo were compared with those taking aspirin, there were no differences in the IMA (100.0% versus 92.1%, p = 0.385) or vein graft (88.8% versus 90.4%, p = 0.675) patency rates. The patency rate, irrespective of treatment, for all IMA grafts was 92.8% (220 of 237) versus 90.1% (345 of 383) for all vein grafts to the LAD (p = 0.309). Thus, both the IMA and vein grafts had excellent patency rates at 1 year. Aspirin did not alter this at 1 year, and there were no differences between IMA and vein graft patency to the LAD.

Aspirin↗

Phase I study of recombinant human tumor necrosis factor alpha in advanced malignant disease.

A phase I study with recombinant human tumor necrosis factor alpha (rhuTNF-alpha; Knoll AG, Ludwigshafen, FRG) in patients with advanced malignant disease was undertaken to evaluate drug toxicity (organ specificity, time course, predictability, reversibility, maximal tolerated dose), effectiveness, antigenicity and pharmacokinetics. TNF was administered as a test dose followed by daily i.v. infusions for 5 days, every 3 weeks (single i.v. infusion lasting 10 min, TNF dissolved in 50 ml 5% human albumin). Dosage was increased in groups of 3 or 4 patients from 0.04 mg/m2 to 0.28 mg/m2. A total of 19 patients with different cancers, including seven large-bowel carcinomas, three chronic myelogenous leukemias, three hypernephromas, two small-cell lung cancers, one malignant melanoma, one malignant lymphoma, one rhabdomyosarcoma and one fibrosarcoma were treated. Major side-effects were chills and fever (maximum 40.4 degrees C, median 38.7 degrees C, 19/19), headache (12/19), nausea and vomiting (12/19) and pronounced (greater than 20%) hypotension (4/19). Acute side-effects could be diminished by paracetamol or indomethacin pretreatment, and with one possible exception no tachyphylaxis to TNF was noted. Mild renal toxicity was seen during TNF treatment. Pharmacokinetic studies showed a serum half-life (t1/2) ranging from 11 min to 17 min for doses from 0.04 mg/m2 to 0.16 mg/m2 and prolonged clearance with t1/2 ranging from 54 min to 70 min in the 0.20-0.28 mg/m2 dose range. No objective antitumor effects were observed in this phase I study.

Adenocarcinoma↗

Saphenous vein graft patency 1 year after coronary artery bypass surgery and effects of antiplatelet therapy. Results of a Veterans Administration Cooperative Study.

To determine whether antiplatelet therapies improve saphenous vein graft patency after coronary artery bypass grafting, we compared 1) aspirin (325 mg once daily), 2) aspirin (325 mg three times daily), 3) aspirin and dipyridamole (325 mg and 75 mg, respectively, three times daily), 4) sulfinpyrazone (267 mg three times daily), and 5) placebo (three times daily). Therapy with dipyridamole and sulfinpyrazone was started 48 hours before bypass graft surgery, and aspirin treatment was begun 12 hours before surgery as a single 325-mg dose. Postoperative treatment was started 6 hours after surgery and continued for 1 year. Graft patency data were obtained early (median, 9 days) and late (median, 367 days) after surgery. The early graft occlusion rate was decreased with all aspirin treatment regimens compared with that of the placebo regimen. At 1 year, in 406 patients with 1,315 grafts, the graft occlusion rate in all of the aspirin groups combined was 15.8% compared with 22.6% for the placebo group (p = 0.029). The patients taking aspirin once daily had a lower occlusion rate (13.2%) compared with the patients receiving placebo (p = 0.050). At 1 year, in the vein grafts placed to vessels less than or equal to 2.0 mm in diameter (804 distal sites), the graft occlusion rate in all of the aspirin groups was 20.1% compared with 32.3% for the placebo group (p = 0.008). In the vein grafts placed to vessels greater than 2.0 mm in diameter (511 distal sites), there was no difference in the occlusion rates between aspirin and the placebo group at 1 year (8.7% vs. 9.0%, p = 0.918).(ABSTRACT TRUNCATED AT 250 WORDS)

Aspirin↗

The statistical analysis of graft patency data in a clinical trial of antiplatelet agents following coronary artery bypass grafting.

Because most coronary artery bypass patients receive more than one graft at surgery, it is most important to determine whether statistical analysis of graft patency should be performed on the premise that the multiple grafts within patients are dependent or independent experimental units. Veterans Administration Cooperative Study No. 207 was a multicenter clinical trial comparing four different antiplatelet regimens to placebo in the prevention of graft occlusion following coronary artery bypass grafting. Using the results from the 1-week postoperative angiograms from the Veterans Administration Cooperative Study No. 207, in which there were 3.2 distal anastomoses per patient, we have tested the hypothesis that grafts within patients tend to act dependently with respect to patency or occlusion by comparing the graft patency data to a binomial distribution (i.e., that distribution that would have been manifest if grafts were independent). Because the graft patency results in Study No. 207 significantly deviated from the binomial distribution (p = 0.0003), a more appropriate analysis for graft patency data was applied using a ratio estimate as applied to cluster sampling. The statistical methods used in 11 previous clinical trials of antithrombotic therapy after coronary artery bypass grafting were examined. Only one of the previous studies used such an analysis, and three additional reports attempted to correct for dependency of grafts within patients in their analyses using other statistical methods. In seven of the studies the investigators did not address the potential problem of a dependent relationship between multiple grafts within patients. We conclude that grafts within patients act as dependent experimental units and that the ratio estimate as applied to cluster sampling may be appropriately applied to these data.

Clinical Trials as Topic↗

Deficiency in interferon production of peripheral blood leukocytes from patients with non-Hodgkin lymphoma.

In search for a rationale for the use of interferons (IFNs) in treatment of non-Hodgkin lymphoma (NHL), we have investigated the IFN system of 13 patients with low-grade NHL, 15 patients with high-grade NHL, and 20 patients with chronic lymphocytic leukemia or leukemic immunocytoma (CLL/IC). Production of IFN induced by phytohemagglutinin (PHA), concanavalin A (Con A), pokeweed mitogen (PWM), Corynebacterium parvum, Herpes simplex virus (HSV), Newcastle disease virus (NDV), and interleukin 2 (IL-2) were studied in the peripheral leukocytes from the patients and from 21 control persons by means of a whole blood technique. All three groups of patients with NHL had significantly reduced production upon stimulation by NDV (p ranged between 0.0038 and less than 0.0001) compared to controls. Similarly, C. parvum also induced lower titers of IFN in the leukocytes of patients with non-leukemic NHL (p = 0.0015 for low-grade NHL and p = 0.0038 for high-grade NHL). When stimulated by PHA, the IFN response of all groups of patients was within normal range. With the exception in low-grade NHL, Con A also induced normal titers of IFN in the patients with NHL. The levels of IFN induced by PWM, HSV, and IL-2 were very low and no differences between controls and patients could be found. As NDV and C. parvum induce mainly IFN-alpha and the mitogens PHA and Con A mainly IFN-gamma, our results suggest that there is a deficiency in the IFN-alpha response in the patients with NHL but normal response in IFN-gamma. This deficiency may have implications for the choice of subtypes of IFN in the treatment of NHL.

Adult↗

Improvement in early saphenous vein graft patency after coronary artery bypass surgery with antiplatelet therapy: results of a Veterans Administration Cooperative Study.

To determine whether specific antiplatelet therapies improved vein graft patency after coronary artery bypass grafting (CABG) we compared (1) aspirin, 325 mg daily, (2) aspirin, 325 mg three times daily, (3) aspirin plus dipyridamole (325 mg and 75 mg, respectively, three times daily), (4) sulfinpyrazone (267 mg three times daily), and (5) placebo (three times daily). Therapy, except aspirin, was started 48 hr before CABG. When aspirin was a treatment, one 325 mg dose was given 12 hr before surgery and therapy was maintained thereafter according to the assigned regimen. Angiographic graft patency data were obtained within 60 days of surgery. Analysis of early graft patency in 555 patients (1781 grafts), revealed the following graft patency rates: aspirin daily, 93.5%; aspirin three times daily, 92.3%; aspirin and dipyridamole, 91.9%; and sulfinpyrazone, 90.2%. All aspirin-containing therapeutic regimens improved (p less than .05) graft patency compared with placebo (85.2%). Chest tube drainage measured within the first 35 hr after CABG revealed that the median loss with aspirin daily (965 ml), aspirin three times daily (1175 ml), and aspirin plus dipyridamole (1000 ml) exceeded (p less than .02) that with placebo (805 ml), while median loss with sulfinpyrazone (775 ml) did not. The reoperation rate was greater (p less than .01) in all the treatment groups that received aspirin (6.5%) compared with the two nonaspirin groups (1.7%). Overall operative mortality was 2.3%, without significant differences among treatment groups. Transient renal insufficiency occurred in 5.3% of patients taking sulfinpyrazone. Thus, early vein graft patency was improved after CABG with all aspirin-containing drug regimens.(ABSTRACT TRUNCATED AT 250 WORDS)

Clinical Trials as Topic↗

Lymphocyte activation and induction of interferon gamma in human leucocyte cultures by the mitogen in Mycoplasma arthritidis supernatant (MAS).

This report succinctly summarizes a number of experiments in which human leucocytes were activated by the mitogen in the supernatant of cultured Mycoplasma arthritidis (MAS). Lymphocytes from a large number of donors were found to be reactive when the two parameters of lymphoproliferation and of production of gamma interferon were analysed. Lymphocytes of cord blood origin were also reactive in lymphoproliferation. Their interferon production was low, but this has been established previously for mitogens in general. During the course of the studies, different batches of MAS were tested, including most recently a purified preparation. All of these were active. Removal of accessory cells adherent to nylon wool column abolished MAS reactivity, whereas it has little effect on lymphoproliferation induced by phytohaemagglutinin (PHA). MAS reactivity was also strongly reduced when monoclonal anti-HLA-DR antibodies were added to the leucocyte cultures.

Bacterial Proteins↗

Oxitropium bromide, a new anticholinergic bronchodilator.

Oxitropium bromide (OB) is a quaternary ammonium congener of hyoscine with anticholinergic properties. We studied its bronchodilating properties in 14 patients with chronic obstructive lung disease without features of asthma in whom theophylline and other bronchodilators were withheld. Five doses of OB(20, 40, 100, 200, and 400 micrograms) as well as 150 micrograms of isoproterenol (ISO) and placebo were administered by metered-dose inhaler on separate occasions in a double-blind fashion. Pulmonary function (flow volume loops and airways resistance), blood pressure, and pulse rate were measured at baseline and periodically for eight hours after drug administration. Onset of bronchodilator effect was within five minutes for OB (P less than .025). Duration of action of OB was at least eight hours (P less than .025). The dose response characteristics of OB were examined by correlating the log dose with the areas under the time-FEV1 curve (r = .97, P less than .01), the time-forced vital capacity curve (r = .98, P less than .01), and the time-SGAW curve (r = .83, P less than 0.1). For FEV1, doses of 40 to 400 micrograms were significantly better than placebo and 100 to 400 micrograms were better than ISO (P less than .01). For forced vital capacity, all doses of OB were better than placebo (P less than .05). For SGAW, the response to the 100- and 400-micrograms doses were significantly better than placebo and isoproterenol (P less than .05). There were no significant effects of OB on pulse, blood pressure, or electrocardiogram. No side effects were noted from the use of OB.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Lymphoproliferative responses of spleen cells of inbred rat strains to Mycoplasma arthritidis mitogen.

A potent mitogen for T lymphocytes of various species has recently been isolated from the supernatant of cultured Mycoplasma arthritidis organisms (MAS). In the mouse, reactivity to this mitogen has been observed to be controlled by the I-E subregion of the major histocompatibility complex. We have analysed the responses of spleen cells from several inbred rat strains covering practically all known haplotypes of the major histocompatibility complex of the rat (RT1). Unlike in the mouse, all of these responded well to MAS, except for the BN rat strain, which is a low responder to all T-cell mitogens, including phytohaemagglutinin and concanavalin A. This unresponsiveness, however, appeared to be unrelated to the RT1 haplotype, since LEW.1N rats carrying the same RT1n haplotype as BN animals responded well. Mice of the strain C57BL/6 are non-responders to MAS, but--as previously shown--their spleen cell responses can be reconstituted by the addition of 2-mercaptoethanol. No such reconstitution was observed for the low responsiveness of BN rat spleen cells. Stimulation with MAS induced high titres of interferon (presumably gamma interferon) in spleen cells from all rat strains tested. Spleen cells from BN rats produced lower interferon activities than those from other strains.

Animals↗

[Experimental studies on various model material. 3. Dimensional behavior and reproductive fidelity as compared to those of elastomers].

Bandless impressions of tooth stumps obtained with the model materials Begolith, Dentaloc, Tewestone, Impredur and Keramid-Cement in combination with the elastic impression materials Silcoflex, Sanal/Silcoflex, Xirux/Xirux F and Impergum were studied in relation to dimensional behavior and reproduction fidelity. With reference to these parameters as well as to the hardness and abrasive behavior of the model materials after processing at various temperatures, recommendations are made for the optimum combination of these two groups of materials in practice.

Acrylic Resins↗

[Experimental studies of various model materials. 1. Comparative study on linear dimension behavior].

The linear dimensional behaviour of the model materials Begolith, Dentaloc, Tewestone, Impredur and Keramik-Cement was investigated at various mixing temperature, the thickness of layer ranging from 3 to 5 mm. It seems that the model materials Begolith, Dentaloc and Tewestone will yield good results in practice. Impredur may be recommended on certain conditions. On the contrary, Keramik-Cement is not suited as a model material.

Dental Materials↗