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Biomedical subjects

J Schaefer

Publications and source records attributed to J Schaefer.

At least 55 records · Page 3Linked to original sources

Relationships between beat-to-beat interval and the strength of contraction in the healthy and diseased human heart.

Twenty-six adult patients, classified by clinical and catheter criteria into groups of those with normal and abnormal left ventricular function, were studied during cardiac catheterization. Right heart pacing was established, and left ventricular dP/dt was measured with end-catheter manometers. By varying the interval preceding a test beat after periods of steady pacing it was confirmed that recovery of left ventricular mechanical function (maximum dP/dt) occurs approximately 800 msec (optimum interval) after a beat. The augmentation of maximum dP/dt of the first 2 beats after an extrasystole, each spaced at the optimum interval, was also studied; the amount of potentiation was varied by alterations in extrasystolic interval. Potentiation decayed from the first to the second postextrasystolic beat with a ratio that was fixed in each individual patient. The ratio (recirculation fraction) was higher in patients with normal than in those with abnormal left ventricular function (mean +/- SD 0.52 +/- 0.10 vs 0.37 +/- 0.11, p less than .005). There was an inverse relationship between this ratio and the degree of potentiation of the first postextrasystolic beat (r = .80, p less than .001). We postulate a disturbance of excitation-contraction coupling mechanisms to explain these effects.

Adult

Direct measurement of peptidoglycan cross-linking in bacteria by 15N nuclear magnetic resonance.

Cross-polarization magic angle spinning 9.12-MHz 15N nuclear magnetic resonance was used to measure the extent of peptidoglycan cross-linking within intact bacterial cells and isolated cell walls of Aerococcus viridans ATCC 10400 grown in the presence of L-[epsilon-15N]lysine. A value of 49% for the cross-linking index was found for normal cells, while for those grown in the presence of low levels of penicillin G (0.1 micrograms/ml), the cross-linking index was reduced to 35%.

Magnetic Resonance Spectroscopy

Lipid bilayer dynamics and rhodopsin-lipid interactions: new approach using high-resolution solid-state 13C NMR.

High-resolution, solid-state 13C NMR spectra have been obtained for unsonicated multilamellar dispersions of 1,2-dilauryl-sn-glycero-3-phosphocholine (DLPC), recombinant membranes containing DLPC and rhodopsin, and native retinal rod disk membranes. The roles of 1H dipolar decoupling, 1H-13C cross-polarization, and magic-angle sample spinning have been investigated. Rotating-frame 13C relaxation times have been measured and are discussed in terms of lipid bilayer dynamics and rhodopsin-lipid interactions.

Fatty Acids, Unsaturated

Electrical and mechanical restitution of the human heart at different rates of stimulation.

Action potential duration and contractility are reduced following premature excitations, and gradually increase as the stimulus interval is lengthened. To examine these phenomena of electrical and mechanical restitution in the human heart, we simultaneously measured action potential duration and the maximum rate of left ventricular pressure in five patients undergoing electrophysiological study. Test beats were introduced at varying intervals after the last of a series of steady state intervals. By plotting action potential duration and maximum rate of left ventricular pressure as a function of the test interval, we formed electrical and mechanical restitution curves. When the rate of steady state pacing was increased, there was a decrease in action potential duration and an increase in the maximum rate of left ventricular pressure for all test intervals; i.e., a change in pacing rate affected action potential duration and maximum rate of left ventricular pressure of test responses in a reciprocal fashion. In addition, a higher steady state pacing rate allowed action potentials and contractile responses to be elicited at shorter test intervals, thereby displacing the electrical and mechanical restitution curves to the left. The magnitude of the leftward shift of both curves corresponded closely to the shortening of the steady state action potential duration induced by the increase in pacing rate. These findings confirm for the human heart that both electrical and mechanical restitution occur after membrane repolarization, i.e., as a function of the electrical diastolic interval preceding a beat, and not the stimulus interval.

Action Potentials

A microagglutination test for human Brucella canis antibodies.

A microagglutination test for the detection of Brucella canis antibodies in humans is described. The use of safranin-dyed B. canis organisms as antigen gave easily interpretable settling patterns and reproducible endpoints. The finding of 18 of 1,147 sera with titers greater than or equal to 1:160 resulted in a presumed false-positive rate of 1.6%. Repeat testing of these positive sera in diluent to which 0.6 m NaCl had been added showed a decrease in titer to less than or equal to 1:40 in eight. Conversely, the increased salt concentration permitted detection of blocking antibodies in two sera which were originally thought to be negative. The test provided serologic evidence for B. canis infection in four patients with otherwise undiagnosed febrile illness. The disease is underdiagnosed due to general lack of serologic testing facilities and misconceptions concerning its prevalence.

Agglutination Tests

Human brucellosis caused by Brucella canis: clinical features and immune response.

Human infection by Brucella canis is not often recognized due to a lack of serious consideration of the disease as a diagnostic possibility. Another factor is the limited availability of specific serologic tests needed in the absence of cross-reactivity between antibodies to B. canis and other Brucella pathogenic to humans. In addition, the organism may not be isolated from blood culture, particularly after antibiotic therapy. We report clinical and laboratory features of four patients with serologically diagnosed B. canis infection and point out the importance of specific serologic testing for B. canis when brucellosis is a diagnostic possibility.

Adult

Estimation of protein turnover in soybean leaves using magic angle double cross-polarization nitrogen 15 nuclear magnetic resonance.

Magic angle cross-polarization 15N nuclear magnetic resonance spectra of intact lyophilized soybean leaves have been obtained at 9.12 MHz. The leaves were harvested over a 6-week period from 15N-uniformly labeled plants exposed to 13CO2 for 1 to 7 days. The concentration of 13C-15N double labels in the main chains of leaf protein was determined nondestructively by double cross-polarization techniques. Both incorporation and turnover rates of these double labels were estimated and together lead to the conclusion that the protein of a mature, fully expanded soybean leaf is fairly long lived, with a half-life of about 30 days.

Kinetics

Comparison of ftorafur with 5-fluorouracil in combination chemotherapy of advanced gastrointestinal carcinoma.

The aim of the study was to compare the combination 5-FU-carmustine with ftorafur-carmustine in the treatment of advanced gastrointestinal cancer. To this end, a prospective, multicenter, randomized trial was initiated. Part I of this trial showed that similar response rates can be obtained with 5-FU-carmustine and ftorafur-carmustine in 109 patients (32.7% versus 26.3%). However, median survival was better in patients treated with 5-FU-carmustine (307 days versus 163 days). Part II of the trial revealed that neither a higher dosage of ftorafur (2 g/m2/day X 5 days) nor the addition of vincristine to both regimens changed the previously obtained results significantly. Again, median survival was found to be better in patients treated with 5-FU combination chemotherapy (304 days versus 144 days). Both the 5-FU and the ftorafur combination were tolerated reasonably well. The results suggest that combination chemotherapy including 5-FU is superior to ftorafur at the applied dosages in terms of survival.

Adult

Different repetition frequencies of a 120 base-pair DNA-element and its arrangement in Chironomus thummi thummi and Chironomus thummi piger.

THe repetition frequency of a highly repetitive DNA sequence has been measured in the genomes of Ch. thummi thummi and Ch, th, piger. This sequence is known to be involved in the evolutionary duplication of defined chromosomal segments leading to a significant increase in the genome size of Ch. th. thummi. Reassociation of this highly repetitive DNA sequence which has a repeat length of 120 base-pairs, with total Ch. th. thummi and Ch. th. piger DNA has shown that the repetition frequency in the Ch, th, thummi DNA is 5.5 fold higher than in Ch, th piger. In both genomes a 120 base-pair sequence is present as tandemly repeated sequence as shown by Southern analysis.

Animals

Simultaneous recording of monophasic action potentials and contractile force from the human heart.

Cardiac monophasic action potentials (MAPs) and contractility have been simultaneously measured in man while the heart rate was being changed by right atrial pacing. A new non-suction electrode was used for safe and long-term recording of MAPs from the endomyocardium. Abrupt changes in cycle-length were followed first by a fast, then a slow response in the adaptation of MAP-duration and of contractility (LV dp/dt max) to the new steady state. After increasing the heart rate then slow phase of MAP shortening appears to be related to the slow staircase of contractility, whereas after the step decrease of frequency no such a relation could be observed. The consistency of these results with those obtained in corresponding in-vitro experiments indicates that this methodical approach may be suitable for assessing the process of E-C coupling in the human heart.

Action Potentials

[A prospective multi-centre study of the response of metastatic gastrointestinal tumours (author's transl)].

In a prospective, multi-centre, randomized study of 109 patients with metastatic gastro-intestinal adenocarcinomas the response rate, survival time and side-effects of two drug combinations, carmustin +5-fluorouracil and carmustin + ftorafur, were compared (same carmustin dosage in both groups). Response to the treatment was 32.7% in those receiving carmustin +5-fluorouracil, 26.3% in those on carmustin + ftorafur. This difference occurred among the 42 patients with gastric adenocarcinoma (33.3% compared with 25%), as well as in 11 with pancreatic adenocarcinoma, and in 56 with colorectal adenocarcinoma (32.1% and 28.6%). Median survival time for 5-fluorouracil + carmustin was 330 days, double that for ftorafur + carmustin (163 days). Bone-marrow toxicity (leukopenia, thrombopenia) was below 10% for both drug combinations. Alopecia occurred in only a few patients. Gastro-intestinal toxicity was common (20% and 18.5%, respectively), but there was no difference between the two groups. The somewhat lower effectiveness of ftorafur compared with 5-fluorouracil was probably due to the deliberately smaller dosage of the former.

Adenocarcinoma

Identification of young megakaryocytes by immunofluorescence and cytophotometry.

The DNA-content of fluoresceine-labeled platelet antigen containing cells of mouse bone marrow was measured. For immunofluorescence highly specific anti-mouse-platelet-serum and fluoresceine-conjugated antigammaglobuline was used, applying the "sandwich" technique. Three hundred panoptically identifable megakaryocytes served as control group. The DNA-polyploidization pattern of megakaryocytes and immunofluorescence positive cells was almost identical. However, among the immunofluorescence positive cells a considerable amount of cells showed DNA-values lower than 4c, whereas the megakaryocytes of the Pappenheim stained smears revealed no DNA-values lower than 4c. The percentages of diploid and tetraploid cells, respectively, was 6 and 7% compared with 0 and 1% of panoptically identifiable megakaryoctyes. The results suggest that young megakaryocytic cells with diploid and tetraploid DNA-values can be detected by immunofluorescence technique, indicating that the flow from the uncommited to the committed megakaryocytic precursor cell appears at this early stage of megakaryocyte production.

Age Factors