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Biomedical subjects

W Wolf

Publications and source records attributed to W Wolf.

At least 109 records · Page 6Linked to original sources
PubMed1986

[Effect of diet and exercise therapy on body weight, performance and lipid metabolism of post-infarct patients during a 4-week rehabilitation program].

From a total of 130 male patients following myocardial infarction a symptom-limited stress cycling ergometer was carried out at the beginning as well as at the end of a 4-week rehabilitation, as well as controls of body weight, the Broca-Index, and Triglyzeride, Cholesterol, HDL-Cholesterol, LDL-Cholesterol and VLDL-Cholesterol fractions. With regard to the Broca-Index, the patients received respectively a 1600 Kcal normal diet (Broca-Index 1.00, n = 34), a 1100 Kcal reductional diet (Broca-Index 1.20, n = 67) and a 600 Kcal reductional diet (Broca-Index 1.32, n = 29). During the whole duration of their stay, the patients underwent a program of physical exercise related to their personal physical performance, which consisted of gymnastic, cycle training, swimming (facultative) and physical training. The improvements of the physical performance were statistically significant, and consisted of 19.4% (normal diet), 18.2% (1100 Kcal diet), namely 11.3% in the 600 Kcal diet group. Weight, Broca-Index and parameters of fat-metabolism remained unchanged under a normal diet. In both reductional diet groups a significant reduction of weight and Broca-Index as well as all blood-fat-metabolism parameters were noted, with the exception of the HDL-Cholesterol fraction, which remained unchanged. Statistical significant correlations between weight reduction, namely increases of physical performance and parameters of blood-fat-metabolism were only noted in cases of a 600 Kcal diet. The noted changes in weight, physical performance and blood-fat-metabolism can be considered as a reduction of the cardiovascular risk profile.

Body Weight↗
PubMed1986

Noninvasive estimation of bound and mobile platinum compounds in the kidney using a radiopharmacokinetic model.

Nephrotoxicity remains a major limitation in the use of cisplatin [cis-diamminedichloroplatinum(II)]. Although several strategies are in use to limit this serious side effect, none is fully satisfactory. Classical pharmacokinetic studies of cisplatin have been based on blood and urine samples. As nephrotoxicity plays a significant role in the design of the therapeutic strategy, the kidneys should be considered as a separate state in any model formulated for ultimate control purposes. Previous studies of organ pharmacokinetics have relied on population measurements. The authors have developed an organ compartmental model from individual animal data obtained noninvasively. The eight-compartment model used to represent the distribution of cisplatin considers free and bound platinum in plasma, platinum in the erythrocytes, mobile and bound platinum in the kidneys, mobile and bound platinum in the tissues, and platinum in the urine. Data were collected from experiments with anesthetized female rats, after intravenous administration of [195mPt]cisplatin. Both arterial and bladder samples, and multiple images obtained with an Anger camera interfaced to a microcomputer were used. The model was estimated from individual data obtained after injection of a bolus of cisplatin (six animals). The model was validated by using it to predict data obtained from forcing the system with a different input function, a 0.5-h intravenous infusion (three animals). The results of this work show that it is possible to noninvasively study drug kinetics in organs that are not readily accessible to direct measurements in an individual, rather than relying on invasive measurements performed on a population.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1986

Criteria for the selection of the most desirable radionuclide for radiolabeling monoclonal antibodies.

Efficient labeling of monoclonal antibodies depends on a number of key factors, mostly related to the characteristics of the radionuclide itself and to the manner of its incorporation into the protein. Such factors include the physical half-life, the photon or particle energy of the radionuclide and its selective deposition of energy in tissues, the method of labeling used (covalent binding or chelation), and the effect that the chemical changes inherent in the labeling process may have on the properties of the protein or of its fragments. The major biological factor in determining the radionuclide of choice for labeling is the projected use of the labeled antibody. When the intended use is diagnostic, then what is required is high-photon density for achieving the high resolution needed for imaging, whereas therapeutic use requires radionuclides with high energy deposition at the target sites, i.e. beta or alpha emitters. A further consideration is to be given to the mode of administration of the radiolabeled monoclonal antibody: determination of the radiopharmacokinetic parameters of compartmental models of biodistribution of the labeled monoclonal antibody and/or its fragments may also assist in selecting which radionuclide may be best to use for radiolabeling a given monoclonal antibody intended for either tumor diagnosis, prognosis and/or therapy.

Antibodies, Monoclonal↗
PubMed1986

Labeling and comparative biodistribution of the monoclonal antibody KS1/4 in nude mice bearing human lung adenocarcinoma.

In order to evaluate some of the key factors that may allow the optimization of radiolabeled monoclonal antibodies for use as diagnostic and therapeutic tools to detect and treat human neoplasia, we compared the biodistribution of the anti-lung-tumor monoclonal antibody KS1/4, labeled with four different radionuclides, in athymic (nu/nu) mice bearing human lung adenocarcinoma. Several radiolabeling methods were used: the first involved coupling a suitable bifunctional chelating agent, such as DTPA, to the KS1/4 monoclonal antibody, followed by binding the radiometal, either 113mIn or 111In. Radioiodination was carried out by the chloramine-T method with 131I, and intrinsic labeling by generating the hybridoma in the presence of 75Se-methionine. An examination of tumors and major organs of mice injected with one of the above radiolabeled KS1/4 MoAbs, and biodistribution at various time intervals up to 96 h post injection revealed that iodination and intrinsic labeling yield the highest tumor uptake. Because of the relatively high deiodination that occurs in vivo, and the high 75Se content in the circulation, the preferential uptake (tumor-to-blood ratio) of these radiopharmaceuticals lags behind the equivalent ratios for the In-labeled MoAb. In the latter group of animals, a second consecutive injection of the labeled MoAb resulted in elevated blood level of radioindium, as well as a corresponding decrease in tumor-to-blood ratios.

Adenocarcinoma↗
PubMed1986

Discharge pattern of single motor units in basal ganglia disorders.

We studied the discharge pattern of motor units (MUs) from the first dorsal interosseous muscle during slight stationary isometric contraction. In six controls, seven patients with parkinsonism, and five patients with choreic disorders, we analyzed 78 MUs. About one-half of the MUs in both patient groups fired irregularly as shown by interval histograms, joint interval histograms, and corresponding statistical calculations. Cross-correlation techniques revealed a characteristic type of MU synchronization in parkinsonism. Analysis of the MU discharge pattern can be useful in clinical assessment of these disorders.

Adult↗
PubMed1986

The contribution of GABA-mediated inhibitory mechanisms to visual response properties of neurons in the kitten's striate cortex.

The effect of the microiontophoretic administration of the GABA antagonist bicuculline methiodide (BMI) on the responses of striate cortical neurons to light stimulation was investigated in kittens ranging in age between 11 and 28 d. The orientation sensitivity of the majority of the 88 neurons tested for this parameter decreased (40%) or was eliminated (18%) following the administration of BMI. Changes were seen in all layers and in all neuronal types, and the proportions of neurons that changed their orientation specificity were about the same during the second, third, and fourth postnatal weeks. Twenty-eight percent of the neurons were not affected in their orientation sensitivity by BMI. These neurons were recorded at all postnatal ages; they were located preferentially in layers IV and VI; and they had unimodal, bimodal, or ON-OFF mixed receptive fields. The remaining 14% of the neurons were initially unresponsive or responded in an erratic way to visual stimulation. These neurons became responsive and even exhibited orientation-specific responses during administration of BMI. The majority (56%) of direction-specific neurons became direction-nonspecific after the administration of BMI. Seventeen percent preserved some direction specificity, whereas 27% did not show any change at all. The effects of BMI on direction sensitivity were seen at all postnatal ages and on all neuronal types throughout layers III-VI. The majority of neurons unaffected by BMI in their direction sensitivity resided in layer VI. In those cases where orientation sensitivity was reduced, direction sensitivity (if present) was usually diminished as well. However, some neurons were found in which only 1 of the 2 parameters was significantly changed by BMI. The spatial structure of the receptive field, as revealed by stationary stimulation, was changed significantly by BMI in about half the neurons tested. A straightforward correlation between the alteration of orientation and/or direction sensitivity and changes in receptive-field structure was not found. The results demonstrate that, in the immature striate cortex, receptive-field properties of many neurons are determined by inhibitory processes mediated by GABA, which may also dictate the actual visual responsiveness of the neurons. The dissociations in the effects of BMI on orientation sensitivity, direction sensitivity, and receptive-field substructure indicate that the synaptic organization responsible for the various functional parameters is unlikely to be the same.

Animals↗
PubMed1986

[Disorders of motor unit discharge activity in parkinsonism].

The discharge activity of single motor units (MUs) of the first dorsal interosseus muscle was recorded in slight stationary isometric contractions. Normal subjects and patients with parkinsonism of various degrees were investigated. The purpose was to study disturbances of the discharge pattern in the patients and their potential diagnostic role. Automatic signal recognition and statistical analysis of the interval distribution were used. Most MUs of the patients revealed considerable irregularities of their discharge sequences best marked by the so called "floating standard deviation". All patients, also 2 without tremor, showed a characteristic synchronization of their MU discharges ("broad-peak" type). Since the above changes were also seen in the patients with only slight symptoms, these investigations, if methodically simplified, could be of diagnostic value.

Action Potentials↗
PubMed1986

Adaptive gain control of saccadic eye movements.

Properties of gain adaptivity in the saccadic system were studied. Subjects had to track a target which moved in single or double steps. The first target step which elicited the primary saccade had an amplitude in the range of 8-16 deg. The primary saccade triggered a further target displacement of 4 deg either in the same or--in different experimental sessions--in the opposite direction of the first target step. These consistent intrasaccadic target displacements lead to adaptive changes of saccadic amplitudes. The experimental data show that the saccadic system adapts to the stimulus sequence in a simple, parametric manner, namely by changing its gain. Consequently, it is assumed that a single gain element determines saccade sizes for all target eccentricities. Further, it is shown that adaptation has different time courses for gain increase and decrease, and its performance is close to completeness. The results are discussed with respect to the undershooting behaviour of goal-directed saccades and the functional demands to the saccadic system.

Adaptation, Ocular↗
PubMed1985

Two new restriction endonucleases DraII and DraIII from Deinococcus radiophilus.

In addition to recently characterized DraI (1), two new Type II restriction endonucleases, DraII and DraIII, with novel site-specificities were isolated and purified from Deinococcus radiophilus ATCC 27603. DraII and DraIII recognize the hepta- and nonanucleotide sequences (sequence in text) The cleavage sites within both strands are indicated by arrows. The recognition sequences were established by mapping of the cleavage sites on pBR322 (DraII) and fd109 RF DNA (DraIII). The sequence specifities were confirmed by computer-assisted restriction analyses of the generated fragment patterns of the sequenced DNA's of the bacteriophages lambda, phi X174 RF, M13mp8 RF and fd109 RF, the viruses Adeno2 and SV40, and the plasmids pBR322 and pBR328. The cleavage positions within the recognition sequences were determined by sequencing experiments.

Bacteriophage lambda↗
PubMed1985

Platelet-adjusted IFN dosage in the treatment of advanced hairy cell leukemia.

It has been demonstrated that hairy cell leukemia (HCL) can be efficiently treated by various preparations of alpha interferons (IFN). Nevertheless, there are several open questions, such as the route, mode and dosage of IFN application. These variables of IFN treatment may be critical since a myelosuppressive effect of IFN, which is commonly seen in the initial phase of treatment, can result in further deterioration of the already impaired platelet production in advanced HCL. The present study shows that serious side effects can be avoided and the flu-like syndromes described by others almost completely reduced by s.c. application of IFN via a portable pump during a daily 8 h period. IFN is initially given five times a week and the daily dose is adjusted according to the actual platelet count. The efficiency controls show that the increase of platelets in the peripheral blood, which is most critical in advanced HCL, may be seen earlier by this than by other protocols, which usually recommend higher daily doses of IFN and only three instead of five weekly applications.

Adult↗
PubMed1985

Comparative radiopharmacokinetics of 18F-5-fluorouracil administered i.v. to rats bearing a mammary tumor.

In an attempt to compare the efficacy of various 5-fluorouracil (5-FU) regimens, we studied the kinetics of 18F-labeled and unlabeled 5-FU in rats. 18F-5-FU was synthesized in our laboratory and was administered in tracer doses to Fischer rats bearing either the 13762 or the R3230 mammary adenocarcinoma, and to Sprague-Dawley rats bearing the Walker-256 carcinosarcoma, with or without pre-treatment with a therapeutic dose of unlabeled 5-FU. In addition, the non-radioactive 5-FU was administered to control rats of both strains. All animals were followed for 70 min either by measuring their 18F blood levels continuously using an extracorporeal blood-loop, or by determining their 5-FU blood levels at discrete time intervals. The biphasic kinetic profile was characterized by determining alpha and beta rate constants and their corresponding half-lives. Differences in 18F elimination, as measured by the area under the curve during the elimination phase, were observed between the pre-treated 13762-bearing rats and the untreated group bearing the same tumor, as well as the pre-treated non-tumored controls and both W-256-bearing groups. Such differences could reveal changes in the ability of those rats to metabolize 5-FU, and hence correlate to the level of active metabolite(s) available to their tumor sites.

Adenocarcinoma↗
PubMed1985

Standardization of CDI-mediated DTPA-coupling to IgG and IgG2a antibodies for 113mIn labeling.

A systematic analysis of various factors involved in the CDI-mediated coupling of DTPA to IgG have been carried out, in order to optimize the labeling yield of a monoclonal antibody labeled to high specific activity. Various CDI-to-DTPA ratios were tested, followed by a range of DTPA (activated) to IgG ratios. Specific activities as high as 600 Ci/mmol could be obtained following labeling with 113mIn, when an IgG : DTPA : CDI ratio of 0.01 : 1:20 was used. Other aspects, such as the volume of each of the reactants, the pH and the reaction times, were also standardized to yield a labeled IgG2a (KS1/4) that could be consistently tested for biodistribution and tumor-binding.

Carbodiimides↗
PubMed1985

Recognition sequences of restriction endonucleases and methylases--a review.

The properties and sources of all known endonucleases and methylases acting site-specifically on DNA are listed. The enzymes are crossindexed (Table I), classified according to homologies within their recognition sequences (Table II), and characterized within Table II by the cleavage and methylation positions, the number of recognition sites on the DNA of the bacteriophages lambda, phi X174 and M13mp7, the viruses Ad2 and SV40, the plasmids pBR322 and pBR328 and the microorganisms from which they originate. Other tabulated properties of the restriction endonucleases include relaxed specificities (Table III), the structure of the restriction fragment ends (Table IV), and the sensitivity to different kinds of DNA methylation (Table V). Table VI classifies the methylases according to the nature of the methylated base(s) within their recognition sequences. This table also comprises those restriction endonucleases, which are known to be inhibited by the modified nucleotides. Furthermore, this review includes a restriction map of bacteriophage lambda DNA based on sequence data. Table VII lists the exact nucleotide positions of the cleavage sites, the length of the generated fragments ordered according to size, and the effects of the Escherichia coli dam- and dcmI-coded methylases M X Eco dam and M X Eco dcmI on the particular recognition sites.

Base Sequence↗
PubMed1985

Assay and time course of 5-fluorouracil incorporation into RNA of L1210/0 ascites cells in vivo.

A method for determination of levels of incorporation of nonradiolabeled 5-fluorouracil (FUra) into RNA (F-RNA) in tissue samples is shown to be applicable to tissues in vivo. BDF1 mice bearing L1210 ascites cells were injected intraperitoneally with [14C]FUra, 100 mg/kg. The time course of F-RNA levels in L1210 cells was determined by following the radiolabeled drug, and by NaB3H4 labeling of isolated and derivatized nucleoside. RNA ribonucleotides were obtained by KOH hydrolysis of perchloric acid precipitates of cell sonicates. FUMP nucleotides were separated from remaining nucleotides by DEAE-cellulose chromatography. FUMP fractions were treated with alkaline phosphatase, and FUrd was separated from non-FUrd nucleoside contaminants by additional DEAE-cellulose chromatography. FUrd was quantitated by periodate oxidation of ribose and NaB3H4 reduction of the resulting nucleoside dialdehydes. Isolation of tritiated FUrd-trialcohol from remaining tissue contaminants and background radioactivity was done by silica gel thin layer chromatography. Comparison of results obtained by isolation of [14C]FUrd with results of NaB3H4 labeling of the same samples showed parallel results with comparable biological standard deviations, although the tritium method consistently gave slightly lower values. The peak level of F-RNA at 3 hr was 1 base substitution per 174 normal nucleotides. The level of F-RNA after 3 hr declined slowly, so that at 96 hr there still remained 1 FUra base per 597 normal nucleotides. Serial determinations of RNA content showed marked decreases, on the basis of either DNA or protein level, that continued up to 96 hr after FUra administration. These biochemical effects are among the most prolonged reported for FUra, suggesting the possibility that F-RNA represents a storage compartment for release of toxic metabolites and emphasize the need for additional study of RNA effects at long time points. Our method for assay of F-RNA appears to be suitable for study of biopsy specimens of tumors and normal tissues following nonradiolabeled-FUra administration.

Animals↗
PubMed1984

Synchronous discharges in pairs of steadily firing motor units tend to form clusters.

Discharges of several motor units (MU) were simultaneously recorded during slight isometric contractions of the first dorsal interosseus muscle using bipolar needle electrodes. Correlograms constructed by counting the relative discharge intervals (1-ms binwidth) between two MU frequently showed narrow central peaks reflecting the occurrence of more synchronies than expected by chance. Diagrams of the temporal distribution of these synchronies revealed that they tend to form clusters consisting of several subsequent events associated with an adjustment of the firing pattern of the two MU. The synchronization described here may be explained by similar mechanisms as the so-called 'short-term synchronization'.

Adult↗