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Biomedical subjects

K Beck

Publications and source records attributed to K Beck.

At least 55 records · Page 3Linked to original sources
PubMed1996

Triple helix formation of procollagen type I can occur at the rough endoplasmic reticulum membrane.

One key problem in understanding the biosynthesis of collagens remains the assembly of the three alpha-chains. How and when are the different gene products selected, aligned, and folded into a triple helix? As the spatial arrangement during biosynthesis might be important, we concentrated on whether the rough endoplasmic reticular membrane is involved in this process. Microsomes were prepared from biosynthetically labeled chick tendon fibroblasts. Vesicles were spread as a monomolecular film which was then transferred over several compartments of a filmbalance containing fresh subphase. Fluorograms of the surface film showed that the monolayer contains procollagen chains. When the monolayer was transferred onto a chymotrypsin/trypsin-containing subphase, the gel bands of the proalpha-chains were shifted into the position of mature alpha-chains, indicating that only the propeptides were digested and the collagenous regions were protected due to triple helix formation. Our results suggest that newly synthesized proalpha-chains can associate as trimers and fold into a triple helical conformation while they are still associated with the membranes of the rough endoplasmic reticulum. These processes also occur when interchain disulfide linkage is inhibited, indicating that chain selection and registration is not dependent on formation of covalent bonds among the carboxyl propeptides.

Animals↗
PubMed1996

The C-terminal domain of cartilage matrix protein assembles into a triple-stranded alpha-helical coiled-coil structure.

Cartilage matrix protein (CMP) is a major component of different cartilages and consists of a disulfide-linked homotrimer. To test whether the C-terminal region forms a three-stranded alpha-helical coiled-coil, we synthesized a peptide, CMP-C36, corresponding to the last 36 residues of human CMP. Analytical ultracentrifugation revealed that CMP-C36 forms a homotrimer under physiological conditions. The sedimentation coefficient of 1.12 S is consistent with a rod-shaped molecule of 5.8 nm length, suggesting a lateral packing of three peptide chains. Depending on conditions, circular dichroism spectroscopy showed 75 to 96% alpha-helical content. The shapes of the spectra are characteristic for a coiled-coil structure. Thermal and guanidine-HCI-induced denaturation revealed a high degree of cooperativity and high stability. The concentration dependence of the melting temperature suggest a two-state transition. The trimer is stabilized by increasing the ionic strength above 130 mM salt, above which six ions are released upon unfolding. The peptide characteristics make it very likely that the C-terminal domain serves as the trimerization site of CMP. The two cysteine residues preceding this sequence region might stabilize the complex after assembly.

Amino Acid Sequence↗
PubMed1996

Mechanism of laminin chain assembly into a triple-stranded coiled-coil structure.

Laminin, a basement membrane glycoprotein, is a heterotrimer with alpha, beta, and gamma chains held together by a triple-stranded alpha-helical coiled-coil structure. Recently, a short peptide sequence at the C-terminus of the alpha-helical domain of each chain was identified as a critical site for the initiation of laminin chain assembly. Synthetic peptides, B1 and B2 (51-mers from the mouse laminin beta 1 and gamma 1 chains respectively) and M (55-mer from the laminin alpha 2 chain), containing these sites were able to assemble into a triple-stranded coiled-coil structure with chain-specific interactions [Nomizu, M., Otaka, A., Utani, A., Roller, P. P., & Yamada, Y. (1994) J. Biol. Chem. 269, 30386-30392]. Here we focus on the mechanism of laminin assembly and examine the conformation and stability of the peptides under various conditions using circular dichroism (CD) spectroscopy. Dependence on chain length for the conformation and stability of trimers suggests that 51-mers for laminin beta 1 and gamma 1 chains and a 55-mer for the laminin alpha 2 chain are critical to attain high thermal stability (T m = 62 degrees C), similar to the larger fragments (approximately 200-mers) and to intact laminins. Since the conformation and stability are dependent on pH and the B1 and B2 monomers and the B1-B2 dimer conformations are partially destroyed at neutral pH, it is likely that they contain intra- and/or interchain repulsions by acidic residues. Moreover, the B1-B2 dimer was significantly more stable under acidic conditions, while the B1-B2/M trimer appears to dissociate into separate B1-B2 and M peptides at pH 2. Urea-induced denaturation showed that the B1-B2/M was more stable than the B1-B2, while both complexes showed virtually identical guanidine hydrochloride denaturation curves. Our data indicate that ionic interactions between B1-B2 and M are critical for the specific trimer formation. We propose a mechanism for laminin assembly: (1) A heterodimer B1-B2 is preferentially formed and creates an acidic pocket which provides a less stable structure due to intra- and intermolecular repulsions between acidic amino acids. (2) A basic site in the M peptide interacts specifically with the acidic pocket of the B1-B2 dimer and results in assembly into a more stable triple-stranded coiled-coil structure.

Amino Acid Sequence↗
PubMed1996

Enteral versus parenteral nutrition: effects on gastrointestinal function and metabolism.

The effects of total parenteral nutrition (TPN) versus enteral nutrition (TEN) were studied in 34 patients following major neurosurgery. Measurements were made of resting energy expenditure (REE), urea production rate (UPR), visceral proteins, parameters of liver and pancreas function, as well as gastrointestinal absorption. To predict nutritional status, nutritional index (NI) was calculated. UPR revealed no significant differences between the groups. After 12 days of TEN, however, synthesis of visceral proteins increased significantly. In addition, NI improved after TEN (p < 0.05), whereas it remained unchanged after TPN. Thrombocyte and lymphocyte counts rose predominately during enteral nutrition. Only in the TEN group was REE increased by 18% and Glasgow Coma Scale (GCS) enhanced from Day 6 on. Exogenous insulin demand was enhanced in the parenterally fed group, and bilirubin (p < 0.05), amylase (p < 0.05), and lipase (p < 0.01) rose significantly, as did gamma-glutamyl-transferase (p < 0.0005) and alkaline phosphatase (p < 0.0005). After 12 d of TPN, vitamin A absorption was significantly attenuated, indicating reduced fat absorption compared to TEN. Carbohydrate absorption did not show significant changes between the groups. Only during TPN did mean values of xylose absorption remain below the normal range. Therefore, enteral nutrition following neurosurgical procedures is associated with an accelerated normalization of nutritional status and an improved substrate tolerance. TEN opposes early postoperative absorption disturbances of the small intestine.

Absorption↗
PubMed1996

Descriptors of breathlessness in cardiorespiratory diseases.

The purposes of this study were: to examine the decriptors of breathlessness chosen by a large sample of patients with cardiorespiratory disease; to determine test-retest reliability of a patient's selection of the descriptors; and to assess whether a patient's recall of the experience of breathlessness is the same as that provoked by physical activity. Questionnaire data were collected at an initial visit for patients who complained of breathlessness and at a second visit in a subgroup of patients. A total of 218 patients who sought medical care for difficulty breathing due to one of seven different conditions were recruited from an outpatient pulmonary disease clinic at a university medical center. Patients selected statements that described qualities of breathlessness from a 15-item questionnaire and completed pulmonary function tests. At a subsequent visit (4 to 15 d later) a subgroup of 16 patients with chronic obstructive pulmonary disease (COPD) repeated the questionnaire at rest (to assess reliability) and after walking in a hallway to provoke a moderate intensity of breathlessness (to compare recall with direct experiences). The relationship among descriptors was evaluated by cluster analysis. The "work/effort" cluster was common for all diagnoses. Each condition was characterized by more than one cluster except COPD. Each diagnosis was associated with a unique set of dusters (e.g., asthma with "work/effort" and "tight," interstitial lung disease with "work/effort" and "rapid" breathing). Percent agreement for all descriptors selected at Visits 1 and 2 (recall) was 79% (r = 0.82; p = 0.001). Percent agreement at Visit 2 between descriptors for recall and for breathlessness provoked by walking was 68% (r = 0.69; p = 0.004). We conclude that patients with different cardiorespiratory conditions experience distinct qualities of breathlessness. Patients' recall of their sensations of breathlessness is reliable and comparable to dyspnea with walking. Employing a questionnaire containing descriptors of breathlessness may help to establish a specific diagnosis and to identify mechanisms whereby a specific intervention relieves dyspnea.

Adult↗
PubMed1995

Acylation of adenylyl cyclase catalyst is important for enzymic activity.

Incubation of human thrombocytes in the presence of [3H]palmitic acid leads to incorporation of this fatty acid into the alpha subunit of Gs as described [Linder et al., Proc. Natl. Acad. Sci. USA 90 (1993) 3675-3679; Degtyarev et al., Biochemistry 32 (1993) 8057-8061] but also into the catalyst of adenylyl cyclase which has not been recognized before. Treatment of labeled membranes with hydroxylamine released the label from both components. Label incorporated into the catalyst could be identified as [3H]palmitate. At the same time chemical deacylation caused partial loss of adenylyl cyclase activity.

Acylation↗
PubMed1995

Studies on canine distemper virus persistence in the central nervous system.

Chronic progressive demyelination in canine distemper virus (CDV) infection is associated with persistence of the virus in the nervous system. We studied persistence by examining expression of CDV mRNA corresponding to all genes of the virus as well as genomic CDV RNA in brain sections of dogs with acute and chronic demyelinating disease. All virus mRNAs were expressed in acute demyelinating lesions in a way similar to that seen in lymphoid tissues, the primary replication site of CDV. Their distribution corresponded very well with immunohistochemical detection of virus protein. In contrast, much more CDV mRNA than virus protein was found in gray matter areas suggesting that translation of CDV can be impaired in nervous distemper. Virus protein and RNA were cleared from chronic inflammatory demyelinating lesions. mRNA corresponding to the distal genes (F; H; L) of CDV disappeared first in inflammatory lesions for technical reasons associated with the particular mode of transcription of morbilliviruses. CDV RNA and protein persisted in chronically ill dogs in other areas of the CNS in which inflammation had not occurred. Our results suggest that persistence of CDV is favored by non-cytolytic spread of the virus and restricted infection of certain cells with reduced viral protein expression. Both tend to delay immune recognition of the virus.

Animals↗
PubMed1994

Sexual behavior of individuals infected with the human immunodeficiency virus. The need for intervention.

BACKGROUND: Public health efforts to stop the spread of the human immunodeficiency virus (HIV) emphasize behavior change among all persons at risk of infection. Yet efficient physician-based intervention might be targeted toward persons infected with HIV. To evaluate the need for intervention among HIV-infected persons attending a continuity clinic, we determined the prevalence of behaviors risky for new transmission of HIV and the characteristics of HIV-infected individuals participating in such behavior. METHODS: Cross-sectional structured survey of 227 HIV-infected patients attending an urban HIV continuity-of-care clinic. RESULTS: Nine percent of the subjects had vaginal, anal, or oral sex without a condom with an HIV-negative last sex partner (24% of whom were unaware that the subject was HIV infected) and an additional 13% with an HIV-status-unknown last sex partner (41% were unaware that the subject was HIV infected). Subjects used a condom for intercourse more often with a partner they knew to be HIV negative than HIV-status-unknown or HIV-positive (84% vs 59% vs 51%). Subjects with more lifetime male sexual partners were more likely to have had sex without a condom with an HIV-negative or HIV-status-unknown partner. CONCLUSION: The HIV-infected individuals in this clinic setting participate in a substantial amount of sexual behavior placing others at risk of new HIV infection. Physicians must address such behaviors, and programs specifically aimed at reducing such behavior should be a public health priority.

Adult↗
PubMed1994

When patients first suspect and find out they are infected with the human immunodeficiency virus: implications for prevention.

To evaluate how individuals infected with the human immunodeficiency virus (HIV) became aware of their infection, when they first suspected they were infected with HIV and factors associated with suspecting HIV infection, we surveyed 227 patients at an urban outpatient HIV clinic. Though nearly all patients acknowledged risk factors for HIV, 60% reported that they did not suspect that they were infected until they received a positive HIV antibody test result. Non-white patients were less likely to suspect HIV infection prior to testing than white subjects (p < 0.03). Subjects not suspecting infection more often received HIV testing through a screening program or during a medical encounter (p = 0.02) and were less likely to be told by others that they might be infected (p = 0.001) than patients suspecting infection prior to testing. Forty-eight percent of subjects who suspected HIV infection prior to testing waited one year or more before obtaining their HIV antibody test. Interventions to reduce faulty personal HIV risk perception are needed to promote earlier HIV diagnosis.

AIDS Serodiagnosis↗
PubMed1994

Sensorimotor synchronization: motor responses to pseudoregular auditory patterns.

Musically trained and untrained subjects (N = 30) were asked to synchronize their finger tapping with stimuli in auditory patterns. Each pattern comprised six successive tonal stimuli of the same duration, the first of which was accented by a different frequency. The duration of inter-stimulus onset intervals (ISIs) gradually increased or decreased in constant steps toward the end of the patterns. Four values of such steps were used in different trials: 20, 30, 45, and 60 msec. Various time-control mechanisms are hypothesized as being simultaneously responsible for subjects' incorrect reproduction of the internal temporal ratios of the stimulus patterns. The mechanism of assimilation (of a central tendency) led subjects to enforce a regular (isochronous) structure on the patterns. The influence of other time-control mechanisms (distinction, subjective expression of an accent, sequential transfer) was expressed mainly in differences between intertap onset intervals (ITIs) and the corresponding ISIs at the beginning of the patterns. The duration of the first two ITIs was in the majority of the trials in an inverse ratio to the ratio of the respective ISIs. The distortions resulting from the timing mechanisms concerned were more pronounced in the performance of nonmusicians than in that of musicians.

Acoustic Stimulation↗
PubMed1993

Ionic interactions in the coiled-coil domain of laminin determine the specificity of chain assembly.

Laminins are a family of large (800 to 900 kDa) multidomain glycoproteins specifically found in basement membranes. They consist of one heavy A chain and two light chains B1 and B2, and several tissue-specific laminin isoforms exist. Chain assembly is mediated through the formation of a rod-like triple-stranded alpha-helical coiled-coil domain about 75 nm long. The interacting edges of the chains are mostly formed by hydrophobic residues in positions a and d of an (abcdefg)n heptad sequence repeat and by a distinct pattern of charged residues in positions e and g. Here, we have analyzed the sequences of known laminin chains in an effort to relate them to interaction potential. Initially, those sequences localized in the long arm were arranged in an optimum heptad-repeating scheme. The interacting edges between chains were then analyzed for interchain hydrophobic and ionic interactions. The short heptad blocks were allowed to shift axially with respect to each other to maximize the number of interactions. The number of hydrophobic interactions was very high and similar for all chain combinations, but especially so for homodimers. As these were not observed experimentally, it seems that hydrophobic interactions probably represent only a prerequisite for coiled-coil formation. The number of ionic interactions, however, directly resembles the interaction potential observed in in vitro experiments. In particular, the number of interchain ionic interactions is high for parallel heterodimer configurations of A and B chains, but low for homodimer arrangements. When the laminin isoform chains, rat s-laminin (B1s) and human merosin (Am), are included in the analysis, they show rather low numbers of mutual interactions but high ionic interaction potentials between them and distinct mouse laminin chains are predicted. For mouse laminin the analysis was extended to a full three-stranded coiled-coil structure. The highest number of interchain ionic interactions occurs for an anti-clockwise chain arrangement of A-->B1-->B2 when viewed from the N terminus. None of the laminin chains appears to be designed for the formation of homodimers, although such conformations are frequently found in other alpha-fibrous proteins.

Amino Acid Sequence↗
PubMed1992

The short-term effects of a fire safety education program for the elderly.

The high risk of fire death and injury among elderly people is well documented. To be effective, fire safety education must reach older adults in the settings in which they reside: nursing homes and other long-term care institutions, board and care homes, and independent living facilities including the person's own home. Training must also be targeted at the people who are responsible for fire safety. In the case of the nursing home or board and care home, the responsible people are the staff and owners. In the case of the majority of older adults who live independently in their homes, it is either the individual or family members. These programs must also be comprehensive. A fire safety education curriculum was developed by a group of experts in a variety of related fields including fire safety, gerontology, health care industry, developmental disabilities, research, and instructional design. Older adults were included in each planning session. Based on that curriculum, workshops and workshop materials were developed for each of the three target populations: staff of health care facilities, staff and owners of board and care homes, and elderly people living independently in their homes. Materials included both print and audiovisuals. A pilot test of each workshop was conducted to test the short-term effects of the programs. Results indicated significant gains in knowledge for all groups and a significant improvement in positive attitudes toward fire safety for most participants. Measures of effects of the programs on intentions to change fire safety practices indicated a potential for change. Results also showed that the measured traits, knowledge of fire safety and attitudes toward fire safety, were relatively stable.

Aged↗
PubMed1992

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↗
PubMed1992

Evaluation of an antibiotic restriction policy using a special drug request form.

At a university teaching hospital, a study was undertaken to assess the frequency and appropriateness of restricted antibiotic use using a special drug request (SDR) form to collect the data. The usefulness of the SDR form itself was also assessed for its ability to provide valuable information about patient care and cost effectiveness. The results of this study are presented below.

Anti-Bacterial Agents↗
PubMed1992

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↗
PubMed1991

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↗
PubMed1991

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↗