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Biomedical subjects

K Beck

Publications and source records attributed to K Beck.

At least 19 recordsLinked to original sources

A truncated laminin chain homologous to the B2 chain: structure, spatial expression, and chromosomal assignment.

We describe the identification of a novel laminin chain. Overlapping clones were isolated from a human fibrosarcoma HT1080 cell cDNA library spanning a total of 5,200 bp. A second set of clones contained an alternative 3' end sequence giving a total of 4,316 bp. The longer sequence contained an open reading frame for a 1,193-residue-long polypeptide. The alternative sequence was shortened at the carboxyl-terminal end coding for a 1,111-residue-long polypeptide. The amino acid sequence contained 21 amino acids of a putative signal peptide and 1,172 residues or alternatively 1,090 residues of a sequence with five distinct domains homologous to domains I-V in laminin chains. Comparison of the amino acid sequences showed that the novel laminin chain is homologous to the laminin B2 chain. However, the structure of the novel laminin chain isolated here differs significantly from that of the B2 chain in that it has no domain VI and domains V, IV, and III are shorter, resulting in a truncated laminin chain. The alternative sequence had a shortened domain I/II. In accordance with the current nomenclature, the chain characterized here is termed B2t. Calculation of possible chain interactions of laminin chains with the B2t chain domain I/II indicated that the B2t chain can replace the B2 chain in some laminin molecules. The gene for the laminin B2t chain (LAMB2T) was localized to chromosome 1q25-q31 in close proximity to the laminin B2 chain gene. Northern analysis showed that the B2t chain is expressed in several human fetal tissues but differently from the laminin B1 and B2 chains. By in situ hybridization expression of the B2t chain was localized to specific epithelial cells in skin, lung, and kidney as opposed to a general epithelial and endothelial cell expression of the laminin B2 chain in the same tissues.

Amino Acid Sequence

A comparison of the effectiveness of three regimens in the prevention of Pneumocystis carinii pneumonia in human immunodeficiency virus-infected patients.

BACKGROUND: Pneumocystis carinii pneumonia (PCP) is a major cause of morbidity and the leading cause of death in patients with the acquired immunodeficiency syndrome. The prevention of the occurrence and recurrence of PCP is a cornerstone in the treatment of patients infected with the human immunodeficiency virus. There are few studies comparing PCP prophylactic regimens. METHODS: The efficacy of three regimens for prophylaxis against PCP was assessed in a retrospective chart review of 211 human immunodeficiency virus-infected patients at risk for the disease. Over the course of the 2-year study period, 133 patients were prescribed trimethoprim-sulfamethoxazole (one double-strength tablet twice a day, thrice weekly) for a mean of 7.4 months (range, 1 to 25 months). Seventy-seven patients received dapsone (50 mg daily) for a mean of 5.7 months (range, 1 to 23 months), and 125 patients received aerosolized pentamidine (300 mg via nebulizer once monthly) for a mean of 9.3 months (range, 1 to 21 months). The majority of patients (62%) received primary prophylaxis; 38% had one or more previous episodes of PCP; and 73% were receiving concomitant antiretroviral therapy. RESULTS: Pneumocystis carinii pneumonia did not develop in any patient receiving trimethoprim-sulfamethoxazole in 981 patient-months. Five patients receiving dapsone for 437 patient-months and 17 patients receiving aerosolized pentamidine for 1166 patient-months developed PCP. Fifty-six percent of the trimethoprim-sulfamethoxazole group and 55% of the dapsone group changed drug due to adverse reactions, while only 2% in the aerosolized pentamidine group required drug change. CONCLUSION: Despite its adverse reaction profile, trimethoprim-sulfamethoxazole is the most effective agent to prevent the occurrence and recurrence of PCP.

Acquired Immunodeficiency Syndrome

Isolation of chick tenascin variants and fragments. A C-terminal heparin-binding fragment produced by cleavage of the extra domain from the largest subunit splicing variant.

The extracellular-matrix glycoprotein, tenascin, consists of disulfide-linked subunits of 190, 200 and 230 kDa (the three splicing variants reported in chicken) and usually exists as a six-armed structure under the electron microscope. We used monoclonal antibodies to isolate and characterize different splicing variants and proteolytic fragments obtained from the native protein. Purified monomeric tenascin has a native molecular mass of 216 kDa and is structured as single arms. Tenascin fragments obtained by pepsin digestion bind to monoclonal antibody (mAb) TnM1 which is directed against epidermal-growth-factor-like repeats in the N-terminal half of all subunits. These fragments represent the thin proximal part of the tenascin arms and they are still partially linked to dimers and trimers via disulfide bridges. Using mAb Tn68, that reacts with a fibronectin-type-III repeat towards the C-terminus, a tenascin fragment, generated by treatment with pronase, can be isolated. Ultrastructurally, this fragment looks like the thicker distal part of the tenascin arms. Only the 230-kDa variant of tenascin gives rise to this distal fragment after cleavage within the alternatively spliced fibronectin-type-III repeats. Native tenascin and all fragments containing the distal part of its arms bind to heparin-agarose, whereas the proximal fragments do not. Oligomeric and monomeric tenascin inhibit fibronectin-mediated fibroblast spreading with comparable efficiency when added to the culture medium, while the proximal fragment has no effect. The distal fragment as well as reduced and alkylated tenascin are active in this assay, but only at higher molar concentrations when compared to the native protein.

Animals

Finger tapping in musicians and nonmusicians.

Timing plays an important role in perceiving and performing music. Finger tapping has been successfully used for analyzing timing processes (Fraisse, 1966, Franĕk et al., 1987, 1988). The aim of this study is to determine differences between musically trained and untrained subjects in their ability to follow repetitive rhythmic tonal patterns by finger tapping. It has been found previously (Povel, 1981; Smith, 1983) that time estimation differs among musicians and nonmusicians under certain conditions. The results presented here show that motor timing revealed by tapping is more accurate in musicians than in nonmusicians.

Fingers

Sensorimotor synchronization: motor responses to regular auditory patterns.

Subjects (N = 32) were asked to synchronize a motor response with tones in auditory patterns. These patterns were created from six tones and six intertone intervals of equal duration. The pitch of the first tone differed from the others. It was found that subjects used three types of timing in their motor response: (1) the first intertone interval was prolonged and the second interval was shortened, (2) the second intertone interval was prolonged and the first interval was shortened, and/or (3) the first interval and the second interval were of approximately the same length. The prolongation of the fifth interval was observed during all three types of timing. The results are explained using the concept of suprasegmental control of timing, which explains a prolongation of intervals at critical control point of the patterns. The occurrence of three different strategies of timing is discussed in connection with similar principles in musical performance.

Acoustic Stimulation

[The significance of hormone receptor content in primary tumors for cytostatic therapy of advanced breast carcinoma].

The influence of the hormone receptor content in the primary tumor on the survival of 83 non-selected patients with advanced breast cancer who underwent cytostatic chemotherapy was investigated. 89% of the patients received anthracycline-containing regimens. There were no significant differences between receptor-positive and receptor-negative patients with regard to the localization of metastases. No survival advantage from the start of chemotherapy was found in the overall group of patients with estrogen-receptor-(ER-)positive and/or progesterone-receptor-(PR-)positive tumors. However, separate analysis of the ER-status revealed a significant survival advantage for patients with positive ER compared to those with negative ER (median survival of 18 months from the start of chemotherapy in ER-positive patients versus 9 months in ER-negative patients). These data indicate that the ER-status in the primary tumor may have an impact on the survival of patients treated with cytotoxic chemotherapy for their advanced disease.

Adult

[Iloprost in the treatment of ischemic tissue lesions in diabetics. Results of a placebo-controlled multicenter study with a stable prostacyclin derivative].

The efficacy of iloprost, a stable prostacyclin analog, was investigated in a placebo-controlled trial in 109 diabetics with ischemic lesions. 56 patients were randomly allocated to iloprost and 53 patients to placebo. Iloprost was intravenously applied for 6 hours daily on 28 consecutive days at an individually tolerated dose up to 2 ng/kg/min. The control group received identical solvent volumes. In addition all patients had an intensive basic, mainly local, therapy. At the end of the treatment in the iloprost group 31 of 50 patients (62%) showed partial (greater than 30%) or total healing of the lesion(s). In the placebo group this was the case in 12 of 51 patients (22.5%). The difference of 38.5% was statistically significant (p less than 0.05, chi 2-test, alpha = 0.05, beta = 0.1). The percentage of patients who were free of pain increased from 23% to 42% (+19%) in the iloprost group and from 38% to 48% (+10%) in the placebo group. After dose-titration iloprost was well tolerated. Flush, headache and abdominal complaints were the most frequent side effects. Heart rate and blood pressure were not influenced and the control of diabetes was not altered.

Adult

Evidence for a specific mechanism of laminin assembly.

The specificity of laminin chain assembly was investigated using fragments E8 and C8-9, derived from the long arm of the molecule, whose rod-like domain consists of the alpha-helical regions of the A, B1 and B2 chains. Urea-induced chain separation and unfolding were monitored by transverse urea/polyacrylamide gel electrophoresis (PAGE) and circular dichroism. Separation of the A and disulphide-linked B1-B2 chains occurred at 3.5-4.0 M urea and by 7.0 M urea all residual alpha-helicity was lost. Removal of urea by dialysis resulted in high recoveries (87-100%) of renatured protein which in its apparent molecular mass, alpha-helix content, chain composition, degree of association and ultrastructural appearance was indistinguishable from native E8. Reduction or reduction and alkylation of the chains did not lead to a decrease in their ability to reassemble specifically. Reformation of the single interchain disulphide, linking the B1 and B2 chains, clearly demonstrates that these chains are correctly aligned in parallel and in register in E8 renatured from its reduced chains. Renaturation of E8 from its reduced and alkylated chains precludes a role for disulphide formation in determining chain alignment but suggests rather than it is involved in the stabilisation of the correctly assembled molecule. These results, together with recent sequence data, provide evidence for the interaction of the alpha-helical regions of the A, B1 and B2 chains in the formation of a triple coiled-coil within the long arm of the molecule. The highly specific nature of this interaction suggests that it is the mechanism by which laminin is assembled in vivo.

Animals

Structure and function of laminin: anatomy of a multidomain glycoprotein.

Laminin is a large (900 kDa) mosaic protein composed of many distinct domains with different structures and functions. Globular and rodlike domains are arranged in an extended four-armed, cruciform shape that is well suited for mediating between distant sites on cells and other components of the extracellular matrix. The alpha-helical coiled-coil domain of the long arm is involved in the specific assembly of the three chains (A, B1, B2, and possible variants) of laminin and is the only domain composed of multiple chains. It is terminated by a large globular domain composed of five homologous subdomains formed by the COOH-terminal part of the A chain. Sites for receptor-mediated cell attachment and promotion of neurite outgrowth reside in the terminal region of the long arm. A second cell attachment site, a cell signaling site with mitogenic action, binding sites for the closely associated glycoprotein nidogen/entactin, and regions involved in calcium-dependent aggregation are localized in the short arms. These domains, which to a large extent are composed of Cys-rich repeats with limited homology to EGF, are the most highly conserved regions in laminins of different origin. At present, most structural and functional data have been collected for a laminin expressed by a mouse tumor, which can be readily isolated in native form and dissected into functional fragments by limited proteolysis. Increasing information on laminins from different species and tissues demonstrates considerable variations of structure. Isoforms of laminin assembled from different chains are focally and transiently expressed and may serve distinct functions at early stages of development even before being laid down as major components of basement membranes.

Amino Acid Sequence

The smoking behaviour of military nurses: the relationship to job stress, job satisfaction and social support.

Three hundred and seven nurses at a large military medical centre were sent and completed an anonymous questionnaire which measured their smoking status along with job stress, job satisfaction and social support, as well as a variety of demographic factors. Three groups of nurses were defined on the basis of their response to the smoking status questions: those who have never smoked (54%), former smokers (23%) and current smokers (22%). The results revealed that the current smokers reported significantly (P less than 0.05) more job stress, job dissatisfaction and less social support than either former smokers or those who had never smoked. Further, the former smokers reported significantly less social support, defined from a variety of perspectives, than those who had never smoked. These were not as important in predicting amount smoked (number of cigarettes per day) among the current smoker group as they were in predicting differences between the different smoking status groups. The results suggest the need to incorporate the issues of social support and to a lesser extent job stress/satisfaction issues into smoking cessation programmes aimed at this population.

Demography

[Experimental udder infection with Escherichia coli. 1. The behavior of selected clinical, hematological and other parameters concerned with milk composition].

Four cows with clinically intact udders in high lactation were intracisternally infected by a pathogenic field strain of Escherichia coli. Infections were induced by quarters and with time intervals. Hence, when the animals were slaughtered six hours from beginning of the experiment, epithelial samples could be collected from cisternal walls and lactiferous ducts which, by the time of sampling, had been in contact with pathogens for one, four, and six hours. Highly acute mastitis began to develop two hours from experimental infection and exhibited typical clinical symptoms, including general disorders, unambiguous alterations to the white blood count, and changes in milk composition. These changes were typical of acute toxin action on the udder quarters. Concomitant reactions of non-infected control quarters, detectable by clinical manifestations or by laboratory diagnosis, were not observed.

Animals

[Prognosis and therapy of kidney carcinoma in a retrospective study in 624 patients].

624 patients, who were treated for carcinoma of the kidney between 1966 and 1987 were analysed in a retrospective study. Prognosis depended in tumor size, lymphatic metastases, and tumor grading. Tumor spread into the renal veins or into the vena cava without lymphatic metastases did not reduce life expectancy. Different symptoms are important as prognostic criteria. Small tumors without spread into the veins can be sufficiently operated from a lumbo costal incision. Preoperative radiation is no beneficial.

Humans

Use of mucosal grafts and temporary tube implants for treatment of teat sinus mucosal injuries.

A mucosal lesion was created in the center of each test sinus of 6 mature, healthy, nonlactating Holstein cows by resecting a circumferential band of mucosa. Each lesion was then treated by implantation of strip grafts of autogenous oral mucosa, temporary silastic tube implant, or a combination of strip grafts and temporary silastic tube implant. All teats were evaluated for patency 6 weeks after treatment, and tube implants were removed through a second thelotomy incision. All teats were reevaluated for gross and radiographic patency 12 weeks after treatment, and teats were collected for histologic evaluation of lesions. All 4 teats treated with grafts only were obstructed at 6 and 12 weeks after treatment. Incomplete coverage of the lesion with mucosa was observed in all 4 teats. The major source of obstruction was proliferation of epithelium and keratin into the lumen. All 8 teats treated with temporary silastic tube implants alone were patent at 6 weeks after treatment, but were obstructed at 12 weeks after treatment. Foci of mucosa at the lesion site were detected in only 2 of the 8 teats. Obstruction resulted from proliferation of granulation tissue into the lumen. All 12 teats treated with grafts and a temporary tube implant were patent at 6 weeks after treatment and 11 of 12 were patent at 12 weeks after treatment, although marked luminal narrowing was evident in 9 of 11 teats. Partial to complete coverage of the lesion with mucosa was seen in all teats. Proliferative granulation tissue, epithelium, and keratin contributed to luminal narrowing in 10 of 11 patent teats. Bacteriologic culture of quarters from 6 of the 11 teats patent at the final evaluation yielded pathogens.

Animals

Two contrary functions of tenascin: dissection of the active sites by recombinant tenascin fragments.

A structural and functional model of tenascin was elaborated using recombinant parts of three alternatively spliced tenascin variants and anti-tenascin monoclonal antibodies. The fusion proteins were compared with intact tenascin for their functions and by electron microscopy. A strong cell binding site was localized within 104 amino acids. This fragment also contains the epitope of the monoclonal antibody anti-Tn68, which inhibits cell attachment to tenascin and binds near the tips of the six arms of tenascin. In contrast, constructs containing the 13 1/2 EGF-like repeats of tenascin showed an antiadhesive effect. The coexistence of the two contrary signals on the same molecule might be responsible for the versatile features of tenascin.

Amino Acid Sequence

Analysis of maple syrup urine disease in cell culture: use of substrates.

Branched-chain 2-oxo acid dehydrogenase activity in human skin fibroblasts against L-leucine, L-valine, L-isoleucine and derived 2-oxo acids was compared in incubations with 1 mmol/l of 1-14C-labelled substrate. The results suggested that the amino acids are the more suitable substrates for an estimation of decarboxylation activity in intact cells. In control cell lines (n = 12), 14CO2 release from amino acids was highest for valine and least for leucine. In a representative number of fibroblast strains of patients with different forms of MSUD (n = 11; residual decarboxylation activity 2-60% of the controls), 14CO2 release from the different amino acids was reduced to a similar degree. Additional measurement of 2-oxo[1-14C]acid release suggested that substrate supply to the branched-chain 2-oxo acid dehydrogenase complex was not rate limiting in the cell lines under investigation.

3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide)

Structural model of vinculin: correlation of amino acid sequence with electron-microscopical shape.

The cytoskeleton-associated protein vinculin exhibits the shape of a 'balloon on a string' when examined by rotary shadowing electron microscopy. Recently, the complete primary structure of chicken vinculin was determined which leads to the questions as to whether the globule might be either hollow or disc shaped, or whether the electron micrographs resemble those of vinculin dimers. Based on a hydrodynamical theory, evidence is presented for the assumption that vinculin as a monomer consists of a compact spherical head 6 nm in diameter connected by a proline-rich domain to a rod-shaped tail about 20 nm in length.

Amino Acid Sequence

[Iloprost, a stable prostacyclin derivative, in stage 4 arterial occlusive disease. A placebo-controlled multicenter study].

The effectiveness of iloprost, a prostacyclin derivative, was assessed in a placebo-controlled multicentre trial on 101 patients with chronic arterial disease, stage IV. All patients were on a basic local treatment, 53 randomly being assigned to the iloprost group, 48 to the placebo one. Both groups received identical saline infusions, one with the other without iloprost. Infusions were given on 28 consecutive days, iloprost being added at a dose of up to 2 ng/kg.min over six hours. At the end of the treatment period, 32 of 52 patients (61.5%) of the iloprost group and eight of the 47 in the placebo group (17%) had partial or complete healing of ulcers (P less than 0.05), the treatment effect persisting in both groups for a mean duration of at least one year. Iloprost was well tolerated, once individual dosages had been appropriately adjusted. Facial flushes, headache and nausea were the most common side effects. Heart rate and blood-pressure variations did not differ between the two groups.

Adult