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Biomedical subjects

M Sieber

Publications and source records attributed to M Sieber.

At least 19 recordsLinked to original sources

Anti-idiotype vaccine against Hodgkin's lymphoma: induction of B- and T-cell immunity across species barriers against CD30 antigen by murine monoclonal internal image antibodies.

Murine monoclonal antibody HRS-4 (Ab1), which defines the cell-bound and soluble CD30 antigen associated with Hodgkin's lymphoma, was used to generate monoclonal anti-idiotypic antibodies (Ab2) in syngeneic BALB/c mice. Murine monoclonal Ab2 14G9 and Ab2 9G10 directed against HRS-4 were shown to be anti-idiotypic Ab2 beta carrying the internal image of the CD30 antigen. These antibodies bound specifically to HRS-4 and effectively inhibited binding of HRS-4 to a CD30 antigen preparation at concentrations as low as 50 ng/ml. KLH-coupled Ab2 beta 14G9 and 9G10 induced in BALB/c mice and New Zealand white rabbits a specific polyclonal humoral response against the 120 kDa band of the CD30 antigen. Moreover, BALB/c mice immunized i.p. with KLH-coupled 14G9 and 9G10 exhibited a statistically significant (p less than 0.01) delayed-type hypersensitivity reaction against CD30 expressing Hodgkin-derived L540-cells. We conclude from these data that Ab2 beta 14G9 and 9G10, mimicking structures of the nominal CD30 antigen, are capable of inducing a CD30-specific T-cell- and B-cell-mediated immune response in mice and even across species barriers in rabbits. These CD30 anti-id antibodies may hold promise for use as vaccines against CD30-antigen-expressing lymphomas.

Animals

Direct and indirect conversion of bull evaluations for yield traits between countries.

Genetic evaluations of Holstein bulls from the US were matched with Canadian, Italian, Mexican, and Netherlands evaluations for the same bulls. Conversion equations for milk yield were computed by least squares, Goddard, and Wilmink methods. Accuracy was assessed by splitting data and applying equations developed from one subset to the other subset. Methods were judged by mean differences between actual and converted evaluations and standard deviation of that difference. Imperfection of conversions appeared to be due to inherent characteristics (variation and bias) of data rather than to inadequacy of conversion methodology. Least squares was slightly better than other methods but is not recommended by the International Bull Evaluation Service. The Goddard method was generally superior to the Wilmink method, but data often are not available for its application. A variation of the Goddard method was equal in accuracy to the Wilmink method. Daughter yield deviation as both dependent and independent variables was examined for only one data set and was little different from the Goddard method. Indirect equations were quite accurate for US to Mexico and US to the Netherlands but much less accurate for US to Italy conversion. Indirect conversions still would be useful until evaluations of bulls in common allow for direct conversions. For all three countries, a variation on indirect methodology was slightly superior to the usual indirect equations.

Animals

Coping strategies and course of disease of breast cancer patients. Results of a 3-year longitudinal study.

In a prospective 3-year longitudinal study investigating correlations between coping strategies and course of breast cancer a consecutive series of 107 patients were assessed for biological and psychosocial data. Data analysis indicated no significant correlations between coping strategies and course of cancer. On the other hand, biological parameters such as size of tumor and lymph node stage at time of surgery correlated significantly with the course of disease. It was concluded that the assessed indicators of coping are of little importance in regard to the course of the disease and less predictive compared with somatical parameters of breast cancer.

Adaptation, Psychological

[Reliability and validity of the Zurich Questionnaire of Coping with Illness].

The coping behavior of three groups of patients (N = 585) was assessed by a 45-item-questionnaire, a revised version of the Zurich Coping Questionnaire (ZKV) published earlier. The following three coping patterns resulted, established by factor analysis: ZKV-1: Depressive coping (Cronbach-alpha = .86), ZKV-2: Self-encouragement/distraction (.81) and ZKV-3: Problem tackling (.60). Retest-stability for the two scales 1 and 3 was high (r greater than .74, 12-month-interval). Concurrent and prognostic validity was assessed. The results indicate that the ZKV is a useful instrument for coping research, especially for the prognostic rating of the subsequent coping behavior.

Adaptation, Psychological

[Positive and negative consequences of voluntary HIV-antibodies test].

Clinical observations and empirical findings with regard to possible negative and positive consequences of the HIV-Antibody-Test are discussed. It was concluded that at the present time we should not recommend the test generally for all people, but rather suggest the way of test-counselling. Results of a pilot study demonstrate that during anonymous testing a conversation about the preceding risk behavior is possible with most of the testes. Recent discussions about aids with the partner or close friends had an important trigger function in their decision to ask for the HIV-Antibody-Test.

AIDS Serodiagnosis

[The significance of psychosocial factors for the course of breast cancer--results of a prospective follow-up study].

The meaning of psychosocial factors for the course of breast cancer--First results of a prospective research project. Studies investigating the meaning of psychosocial factors for the course of cancerous diseases have so far been contradictious. In this paper the basic datas and first results of a prospective research project on this topic covering 107 breast cancer patients are reported. Somatic datas such as stage of lymph-nodes, type of surgery and additional treatments (radiation therapy or chemotherapy), are less important for the coping process 6 months after primary treatment than the cognitive attitudes of the patients toward their disease. About 56 percent of the patients coped quite well with their disease, 44 percent showed difficulties. The group of patients whose somatic and psychosocial prognosis was judged rather unfavorably at the time of the first examination, showed the highest rate of recidivation and progredience in the follow-up of the first 12 months.

Adaptation, Psychological

Calcium channels reconstituted from the skeletal muscle dihydropyridine receptor protein complex and its alpha 1 peptide subunit in lipid bilayers.

In the first part of this study, we show that sDHPR and pDHPR preparations reconstituted into lipid bilayers formed on the tips of patch pipettes exhibit two divalent cation-selective conductance levels of 9 and 20 pS, similar in single-channel conductance to VSCC reported in a variety of intact preparations (see Pelzer et al. and Tsien et al. for review). The larger conductance level is similar to the VSCC identified in intact rat t-tubule membranes and described in sDHPR and pDHPR preparations, and shares many properties in common with activity from L-type VSCC. It is sensitive to augmentation by the DHP agonist (+/-)-BAY K 8644 and cAMP-dependent phosphorylation, and to block by the phenylalkylamine (+/-)-D600 and the inorganic blocker CoCl2. Its open-state probability and open times are increased upon depolarization as expected for a voltage-dependent activation process. Upon depolarization beyond the reversal potential, however, open-state probability and open times decline again. A reasonable way to explain the bell-shaped dependence of open times and open-state probability on membrane potential is to assume voltage-dependent ion-pore interactions that produce closing of the channel at strong negative and positive membrane potentials. By contrast, the smaller conductance level may be similar to the 10.6-pS t-tubule VSCC described by Rosenberg et al. and may best be compared with T-type VSCC. It is largely resistant to augmentation by (+/-)-BAY K 8644 and cAMP-dependent phosphorylation or block by (+/-)-D600, but is sensitive to block by CoCl2. Its open times and open-state probability show a sole dependence on membrane potential where depolarization increases both parameters sigmoidally from close to zero up to a saturating level. Both elementary conductance levels do not exhibit significant inactivation over a wide potential range, which may suggest that skeletal muscle VSCC inactivation is either poorly or not voltage-dependent at all. This possibility seems in agreement with bilayer recordings on reconstituted intact t-tubule membranes and voltage-clamp recordings on intact fibers. It supports the idea that the decline of Ca2+ current in intact skeletal muscle fibers may be due to Ca2+ depletion from the t-tubule system and/or to inactivation induced by Ca2+ release from the sarcoplasmic reticulum. We consistently observe two conductance levels of 9 and 20 pS, either singly, or together in the same bilayer from solubilized DHPR samples and even highly purified DHPR preparations.(ABSTRACT TRUNCATED AT 400 WORDS)

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy

Effects of body measurements and weight on calf size and calving difficulty of Holsteins.

Body measurements (heart and paunch girths, wither height, chest depth, pelvic length and width, and body length), body weight, and calving evaluation data (calf birth weight, calf sex, calf presentation, and calving assistance needed) were collected from 1974 parities of 762 Holstein cows between 1968 and 1986. Degree of calving assistance was scored continuously from 1 (no assistance) to 10 (hard mechanical assistance). Phenotypic correlations of dam body traits with calf birth weight were all significantly positive when combined for all parities and ranged from .23 for paunch girth to .27 for body weight and heart girth. Correlations of dam body traits with calving assistance scores were all significantly negative across parities and ranged from -.24 to -.30. Correlations of calf birth weight with calving assistance were higher for first parity (.37) than for all parities (.20). Least squares analysis showed that cows with shorter wither height and shorter pelvises tended to require more calving assistance. Heavier calves, winter calvings, and earlier parity all were related to increased dystocia. Male calves were heavier than female calves and also were associated with greater calving difficulty.

Animals

[The significance of somatic and psychosocial factors for coping with illness by patients with multiple sclerosis].

The coping behavior of 298 multiple sclerosis patients was assessed by means of a questionnaire. Despite more pronounced somatic complaints, women view their psychological situation more positively than men; they are more optimistic, less anxious, less depressed, and less preoccupied with their illness and its consequences. In the event of reduced working capacity due to the disease, men are more frequently disabled than housewives. However, there is evidence that early disability compensation may have a negative effect on the psychological well-being and the coping behavior. Careful thought should therefore be given to the timing when the question of a pension is discussed.

Adaptation, Psychological

cAMP-dependent protein kinase rapidly phosphorylates serine- 687 of the skeletal muscle receptor for calcium channel blockers.

The cAMP-dependent phosphorylation of the 165-kDa subunit of the receptor for organic calcium channel blockers (CaCB-receptors) was studied. Tryptic peptide analysis showed that cAMP-dependent protein kinase phosphorylates rapidly a serine in one peptide. Up to three peptides containing phosphoserine and -threonine are phosphorylated in a 2-h incubation. The isolated 165-kDa subunit was digested with trypsin and the endoproteinase Lys-C and Glu-C. The rapidly phosphorylated peptide was isolated from each digest. The amino acid sequence was determined by Edman degradation and compared with the deduced amino acid sequence of the CaCB-receptor from rabbit skeletal muscle (Tanabe, T., Takeshima, H., Mikami, A., Flockerzi, V., Takahashi, H., Kangawa, K., Kojima, M., Matsuo, H., Hirose, T., and Numa, S. (1987) Nature 238, 313-318). Phosphoserine was determined as the phenylthiohydantoin-derivative of dithiothreitol-dehydroalanine. The phosphorylated serine was identified as Ser-687 which is localized between the transmembrane regions II and III. A second phosphopeptide was isolated into which phosphate was incorporated into Ser-1617 with a slow time course. This peptide is located in the COOH-terminal cytoplasmic domain of the 165-kDa subunit. It is anticipated that phosphorylation of serine 687 affects the opening probability of the calcium channel.

Animals

Rabbit skeletal muscle microsomes contain two distinct phenylalkylamine-binding sites.

Lu49888, a photoaffinity analog of verapamil, was used to identify specific binding sites for phenylalkylamines of calcium channels present in rabbit skeletal muscle microsomes. Direct binding equilibrium measurements and displacement curves of Lu49888 by its non-radioactive analog yielded an apparent single class of binding sites with Kd and Bmax values of 16.5 nM and 7.5 pmol/mg respectively. Lu49888 was specifically incorporated into three proteins of apparently 165 kDa, and 33 kDa. Incorporation into the 55-kDa protein was blocked by 10--50-fold higher concentrations of unlabeled phenylalkylamines compared to incorporation into the 165-kDa protein, suggesting that the 165-kDa and 55-kDa proteins contain a high and a low-affinity verapamil-binding site respectively. The photoaffinity-labeled proteins were solubilized by 1% digitonin or 1% Chaps in roughly equal amounts. The 165-kDa protein bound to wheat-germ-agglutinin(WGA)--Sepharose and sedimented in sucrose density gradients with the same constant as the purified dihydropyridine receptor, which has been reconstituted to a functional calcium channel. The 55-kDa membrane protein did not bind to the WGA-Sepharose column and sedimented in sucrose density gradients with a lower s value than the 165-kDa protein. The 165-kDa but not the 55-kDa membrane protein was specifically labeled by azidopine, the photoaffinity analogue of dihydropyridines. The 55-kDa protein of the purified dihydropyridine receptor was not significantly labeled by Lu49888 showing that the 55-kDa protein of the membrane is unrelated to the purified high-affinity dihydropyridine receptor.

Affinity Labels

The biochemical properties of L-type calcium channels.

Activation of the cardiac beta-adrenergic receptor stimulates cAMP levels and activates cAMP-dependent protein kinase. The kinase phosphorylates the calcium channel and enhances thereby the availability and the number of channels that are opened during depolarization. The increased calcium influx leads then to a positive inotropic response. The calcium channel can be identified in vitro by organic calcium channel blockers, which bind stereoselectively to a high affinity, low capacity site localized in sarcolemma and junctional sarcoplasmic reticulum. This binding site has been purified from skeletal muscle microsomes. The purified receptor contains three peptides of Mr 165, 55, and 32 kDa in stoichiometric amounts. The high affinity binding sites for dihydropyridines and phenylalkylamines are localized on the 165 kDa peptide. This peptide is phosphorylated up to 2 mol/mol by cAMP-dependent protein kinase. Reconstitution of the purified receptor yields a calcium channel that has many properties of the cardiac L-type calcium channel. It is suggested that these properties are confined to a 165 kDa peptide in skeletal muscle and to a 183 kDa peptide in cardiac muscle.

Animals

Comparison between factor analysis from a phenotypic and genetic correlation matrix using linear type traits of Holstein dairy cows.

Data on 18 linear type scores and production data for 43,428 records by 228 sires were used to compare two different factor-analyses procedures. Using a genetic correlation matrix to obtain a genetic factor matrix showed that the number of derived factors could be reduced to seven genetic factors vs. eight phenotypic factors. Genetic factors provided a good summary of the data and accounted for 79.3% of the total variation vs. 69.1% expressed by eight phenotypic factors. A comparison between the use of a genetic and phenotypic multiple regression analysis showed some difference for the basic rank of factor influence on production and herdlife.

Animals

Phosphorylation of the purified CaCB-receptor.

The purified receptor for calcium channel blockers (CaCB-receptor) from rabbit skeletal muscle contains three polypeptides within a molecular mass of 165, 55, and 32 kDa. cAMP-dependent protein kinase was shown to phosphorylate preferentially the 165-kDa protein. The major phosphorylation site was identified and compared with the recently published primary sequence of the CaCB-receptor. It is concluded that serine 687 is the phosphorylation site. Phosphorylation of serine 687 may regulate the open-state probability of the CaCB-receptor.

Animals

Phosphorylation of the purified receptor for calcium channel blockers by cAMP kinase and protein kinase C.

The dihydropyridine receptor purified from rabbit skeletal muscle contains three proteins of 165, 55 and 32 kDa. cAMP kinase and protein kinase C phosphorylate the 165-kDa and the 55-kDa proteins. At identical concentrations of each protein kinase, cAMP kinase phosphorylates the 165-kDa protein faster than the 55-kDa protein. Protein kinase C phosphorylates preferentially the 55-kDa protein. cAMP kinase incorporates up to 1.6 mol phosphate/mol protein into the 165-kDa protein and 1 mol/mol into the 55-kDa protein upon prolonged incubation. At a physiological concentration of cAMP kinase 1 mol phosphate is incorporated/mol 165-kDa protein within 10 min, suggesting a physiological role of this phosphorylation. Protein kinase C incorporates up to 1 mol phosphate/mol into the 55-kDa protein and less than 1 mol/mol into the 165-kDa protein. Tryptic phosphopeptide analysis reveals that cAMP kinase phosphorylates two distinct peptides in the 165-kDa protein, whereas protein kinase C phosphorylates a single peptide in the 165-kDa protein. cAMP kinase and protein kinase C phosphorylate three and two peptides in the 55-kDa protein, respectively. Mixtures of the tryptic phosphopeptides derived from the 165-kDa and 55-kDa proteins elute according to the composite of the two elution profiles. These results suggest that the 165-kDa protein, which contains the binding sites for each class of calcium channel blockers and the basic calcium-conducting structure, is a specific substrate for cAMP kinase. The 55-kDa protein apparently contains sites preferentially phosphorylated by protein kinase C.

Animals

The 165-kDa peptide of the purified skeletal muscle dihydropyridine receptor contains the known regulatory sites of the calcium channel.

The dihydropyridine receptor purified from rabbit skeletal muscle yields in the presence of dithiothreitol and sodium dodecyl sulfate on polyacrylamide gels bands of apparent molecular mass 165 +/- 5, 130 +/- 5, 55 +/- 3, 32 +/- 2 and 28 +/- 1 kDa (chi +/- SEM, n = 12). Under nonreducing conditions, the 130 kDa and 28-kDa peptides migrate as a single peptide of 165 kDa. These peptides were separated on a HPLC size-exclusion column. The specific absorption coefficients of the isolated peptides were determined. From these a stoichiometry of 1:1.7 +/- 0.2:1.4 +/- 0.3 (chi +/- SEM of 12 experiments with three different preparations) was calculated for the 165-kDa, 55-kDa and 32-kDa peptides. The relative amount of the 130/28-kDa peptide varied with different preparations. Tryptic, chymotryptic and V-8 protease peptides of the isolated proteins suggested that the 130/28-kDa peptide was not related to the 165-kDa peptide. The dihydropyridine photoaffinity analog (+/-)-azidopine was specifically incorporated only into the 165-kDa peptide with an efficiency of about 2.4%. The azido analog of desmethoxyverapamil, LU 49888, was specifically incorporated into the same peptide with an efficiency of 1.5%. These results suggest that only the 165-kDa peptide contains the regulatory sites detected so far in the voltage-operated L-type calcium channel. They suggest further that the 130/28-kDa peptide, which migrates as a 165-kDa peptide under nonreducing conditions, does not contain high-affinity binding sites for the calcium channel blockers.

Affinity Labels

Factor analysis for evaluating relationships between first lactation type scores and production data of Holstein dairy cows.

Data on linear type scores for 18 traits from evaluations from Twenty-First Century Genetics from September 1979 to December 1983 were matched against the DHIA production records. Data for production were 43,428 records by 228 sires, each with at least 20 progeny in at least nine herds. Data were randomly split to analyze and validate the investigation of factor analyses to relate type scores and production. Type scores (1 to 50 points) were adjusted for days in milk and age at first calving. Means of the adjusted type scores ranged from 25.2 to 31.7 (+/- 5.39 to 9.09 SD). A principal component analysis showed that the first eight components accounted for more than 69% of the total variance in type scores. A principal factor analysis followed by a factor rotation was used to define new factors. Multiple linear regression on these factors indicated that herdmate deviation milk and fat are more closely related to characteristics of the mammary system than they are to body traits. For herdlife analyses, using 17,288 records, cows with well-attached udders stayed in herds longer.

Animal Husbandry