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Biomedical subjects

J Saarinen

Publications and source records attributed to J Saarinen.

At least 19 recordsLinked to original sources
PubMed1995

Proteolysis and fusion of low density lipoprotein particles strengthen their binding to human aortic proteoglycans.

Lipid droplets resembling those seen in the extracellular space of the arterial intima were generated in vitro when granule proteases of rat serosal mast cells degraded the apolipoprotein B-100 (apoB-100) component of granule-bound low density lipoprotein (LDL), and the particles fused on the granule surface (Paanenen, K., and Kovanen, P. T. (1994) J. Biol. Chem. 269, 2023-2031). Moreover, the binding of the fused particles to the heparin proteoglycan component of the granules was found to be strengthened. We have now treated LDL particles with alpha-chymotrypsin and examined the strength with which the proteolytically modified LDL binds to human aortic proteoglycans on an affinity column. We found that chymotryptic degradation of the LDL particles triggered particle fusion. The higher the degree of proteolytic degradation, the higher were the degree of fusion and the strength of binding to the aortic proteoglycans. Separation of the proteolyzed particles by size exclusion chromatography into two fractions, unfused and fused particles, and analysis of their binding strengths revealed that not only the fused but also the unfused proteolyzed particles bound more tightly to the proteoglycans than did the native LDL particles. To investigate the mechanism underlying this increase in binding strength, we attached [13C]dimethyl groups to the lysines and used NMR spectroscopy to quantify the active lysine residues of apoB-100, which are thought to be located in basic areas of apoB-100 and involved in binding of LDL to proteoglycans. Analysis of the 13C-labeled particles showed that, despite loss of apoB-100 fragments from the particles, the number of active lysine residues in the unfused proteolyzed particles had not decreased. In the fused proteolyzed particles, the number of active lysine residues was markedly increased. Thus, proteolytic fusion appears to increase the number of basic domains of apoB-100, which would explain the observed increase in the strength of binding of the modified LDL particles to arterial proteoglycans. Since the fused particles resemble the small lipid droplets found in the atherosclerotic arterial intima, this LDL modification offers a plausible mechanism for the focal accumulation of lipid droplets in the extracellular proteoglycan matrix during atherogenesis.

Aorta↗
PubMed1995

Human mast cell chymase and leukocyte elastase release latent transforming growth factor-beta 1 from the extracellular matrix of cultured human epithelial and endothelial cells.

Monolayer cultures of human epithelial and endothelial cells were used to study the association of latent transforming growth factor-beta 1 (TGF-beta 1) to extracellular matrices and its release and activation during matrix degradation. Human umbilical vein endothelial cells and embryonic lung fibroblasts produced relatively high levels of TGF-beta 1, its propeptide (beta 1-latency-associated protein), and latent TGF-beta-binding protein and incorporated latent TGF-beta 1 into their matrices as shown by immunoblotting. Amnion epithelial cells produced lower levels of these proteins. Confluent cultures of epithelial cells were exposed to matrix-degrading proteases and glycosidases. Mast cell chymase, leukocyte elastase, and plasmin efficiently released matrix-bound latent TGF-beta 1 complexes, while chondroitinase ABC and heparitinases were ineffective. The ability of the proteases to activate recombinant latent TGF-beta 1 was tested using growth inhibition assays and a novel sodium deoxycholate-polyacrylamide gel electrophoresis followed by immunoblotting. Sodium deoxycholate solubilized M(r) 25,000 TGF-beta 1 but did not dissociate high M(r) latent TGF-beta 1 complexes, allowing separation of these forms by polyacrylamide gel electrophoresis. Mast cell chymase and leukocyte elastase did not activate latent TGF-beta 1, suggesting that its release from matrix and activation are controlled by different mechanisms. The release of TGF-beta from the matrix by leukocyte and mast cell enzymes may contribute to the accumulation of connective tissue in inflammation.

Amnion↗
PubMed1995

Perceptual learning in vernier acuity: what is learned?

It has been suggested that the improvement of vernier acuity in the course of practice reflects "fine tuning" of the visual mechanisms underlying vernier acuity. Masking studies suggest that an important source of information by which the visual system may accomplish fine vernier acuity is the activity in orientation tuned channels. Therefore, we investigated whether improvement in vernier acuity after training was accompanied by systematic changes in the orientation tuning characteristics of vernier acuity (as revealed by simultaneous spatial noise masking). The results show large interindividual variation in learning vernier acuity. However, they reveal a close correspondence between the improvement in vernier acuity and the narrowing of the orientation tuning function. Thus, the results provide some support for the notion of narrowing of the orientation characteristics of vernier acuity in the course of learning.

Humans↗
PubMed1995

Visual search at different spatial scales.

Treisman and Gelade's (1980) feature-integration model claims that the search for separate ("primitive") stimulus features is parallel, but that the conjunctions of those features require serial scan. Recently, evidence has accumulated that parallel processing is not limited to these "primitive" stimulus features, but that combinations of features can also produce parallel search. In the experiments reported here, the processing of feature conjunctions was studied when the stimulus features of a combination were at different spatial scales. The patterns in the search array were composed of three cross-shaped or T-shaped (local) elements, which formed an oblique bar (the global pattern) 45 deg or 135 deg in orientation. When the target and distractors differed from each other at one spatial scale only (either in the bar orientation or in the shape of the local elements), target detection was independent of the number of distractors, i.e., the search was parallel. In the conjunction task, in which the target and distractors were defined as the combinations of the bar orientation and the element shape, i.e., both spatial scales were relevant, the detection of the target required slow serial scrutiny of the search array. It is possible that the conjunction search could not be performed in parallel because switches between the two scales (or spatial frequency channels) are linked to attention and the task required the use of both scales in order to find the target.

Adult↗
PubMed1995

Ideological and logistical barriers to the development of nursing research: real or imagined?

Australian nurses sit amidst a treasure-trove of developing knowledge, and yet are dragging their feet when it comes to nursing research. Barriers or 'perceived' barriers to the development of nursing research in this country are explored. These include ideological concerns, economic constraints, and infrastructural factors. A set of recommendations, which may assist nurses in attaining a research profile in keeping with the status of a profession is offered.

Attitude of Health Personnel↗
PubMed1995

The incidence of postoperative deep vein thrombosis in vascular procedures. FINNVASC Study Group.

This survey aimed to estimate the rate of deep venous thrombosis (DVT) in an unselected population treated for peripheral vascular diseases. The study comprised 7533 patients on the nationwide Finnish vascular registry (FINNVASC) during two-years study period. Thirty-four (0.45%) patients were reported to have a postoperative thrombosis. Thirty-two (94%) of these had undergone vascular procedures involving the infrarenal aorta or arteries in the lower extremities. There was no difference in the occurrence of determinants (diabetes, hypertension etc.) when the group with postoperative DVT was compared to the rest of the patients on the registry. The procedures involving the lower extremity seem to carry a higher risk of postoperative DVT. In this type of surgery special attention should be focused on DVT prophylaxis.

Adolescent↗
PubMed1994

Activation of human interstitial procollagenase through direct cleavage of the Leu83-Thr84 bond by mast cell chymase.

In inflamed tissue sites characterized by on-going matrix degradation, the matrix metalloproteinases are secreted as latent precursors which are capable of proteolysis only after extracellular activation. Such areas often contain locally increased numbers of mast cells capable of releasing complexes between heparin proteoglycans and fully active endopeptidases with either tryptic (tryptase) or both tryptic and chymotryptic (chymase) activity. We have examined the ability of purified human skin chymase to activate human interstitial procollagenase (matrix metalloproteinase-1) in the absence and presence of heparin, the physiologic associate of chymase. Our studies indicate that chymase activates procollagenase in a time- and concentration-dependent manner. Heparin was found to increase markedly the rate at which chymase activates procollagenase both by accelerating the cleavage of procollagenase and also by preventing its further degradation. Moreover, we found that chymase activates procollagenase directly by cleaving the Leu83-Thr84 bond, without formation of any intermediate species. This is a novel mechanism for procollagenase activation, which contrasts sharply with the activation mechanisms of other activators studied so far. The ability of chymase to activate procollagenase suggests that chymase plays an active role in matrix degradation at tissue sites where mast cells coexist with extracellular procollagenase.

Amino Acid Sequence↗
PubMed1994

Temporal integration of auditory information in sensory memory as reflected by the mismatch negativity.

Event-related potentials (ERPs) to different types of infrequent change in a tone pair composed of two closely spaced tones of different frequencies were recorded. The mismatch negativity (MMN), a change-specific component of the ERP, was elicited by reversing the order of the two tones, by repeating the first tone, by replacing the first tone with the second tone, or by omitting the second tone. The omission of the second tone, however, elicited the MMN only when the interval between the two tones was very short (offset to onset 40 or 140 ms) but did not when this interval was somewhat longer (240 or 340 ms). The pattern of the present results suggests that sensory-memory traces, as reflected by the MMN, integrate information about two closely spaced stimuli into a unitary sensory event.

Adult↗
PubMed1994

Visual search for global and local stimulus features.

The observer looked for a target pattern differing from distractors in orientation at one spatial scale only (either at a global or at a local scale) and ignored the other. The stimulus patterns in the search array were vertical or horizontal bars consisting of four oblique line segments sharing the same orientation (45 degrees or 135 degrees). In the search at the global scale, the target and distractors differed from each other in the bar orientation, but not in the orientation of the line segments, which was random. In the search at the local scale, the observer had to use the line orientation for discriminating the target and distractors (the bar orientation was random). The results showed that even though the search was parallel at both scales (ie the search time did not increase with an increasing number of distractors), target detection at the local scale required considerably more time than at the global scale. This latter finding is in agreement with the phenomenon of 'global precedence'.

Adult↗
PubMed1993

Focal visual attention and pattern discrimination.

Pattern discrimination in the presence of distractor patterns is improved when the stimulus display is preceded by a precue designating the location of the target pattern. Experiments were conducted to determine how big an improvement the precue produced. The specific question of whether the observer is able to process selectively the stimulus pattern in the cued location of the display and ignore the patterns of the noncued locations was addressed. In order to study this, reaction time for pattern discrimination on a blank background (no distractors) was compared with the reaction time when the observer performed the same discrimination task in the presence of distractors and a precue had indicated the location of the stimulus pattern to be discriminated. The results showed that these two reaction times were equal if the cue preceded the stimulus patterns at intervals which were longer than some minimum time. Hence, stimuli outside the 'aperture' of focal attention can be ignored. These results could not be attributed to eye movements, because the longest duration of the whole sequence of precue and stimulus patterns was only 200 ms.

Adult↗
PubMed1993

Focal attention and the perception of pattern structure in extrafoveal vision.

Several studies have shown that visual attention enhances the encoding of the positional relationships between pattern elements, i.e., the perception of pattern structure. This theoretical note discusses the possibility that the inferiority of extrafoveal vision in the perception of pattern structure results, at least partially, from less effective focal attention in the periphery. Hence, there may exist higher level differences between foveal and extrafoveal vision in information processing which cannot be explained by the spatial inhomogeneity of the retino-striate system.

Attention↗
PubMed1993

A rapid method to study heterogeneous gene expression in liver by direct assay of messenger RNA from periportal and perivenous cell lysates.

To study zonation of liver gene expression, we obtained periportal or perivenous rat liver cell lysates virtually devoid of nuclear material by site-directed digitonin infusion in situ. Total RNA was isolated, messenger RNAs were reverse transcribed and complementary DNAs were assayed after polymerase chain reaction-mediated amplification. The zonal distribution of messenger RNAs of alcohol dehydrogenase (little zonation), glutamine synthetase (perivenous) and cytochrome P-450 2E1 (perivenous) messenger RNAs, as analyzed by this technique, were found to be similar to the distribution of corresponding apoproteins. Using appropriate primers or complementary DNAs, zonation of many different messenger RNAs can be determined from the same sample by this simple and rapid method.

Animals↗
PubMed1992

Representation of abstract attributes of auditory stimuli in the human brain.

Representations of abstract attributes of auditory stimuli in the human brain were demonstrated using the mismatch negativity (MMN), an event-related potential component elicited by a change in a repetitive sound. Stimuli were pairs of sinusoidal tones. There were two types of tone pairs in each block, standard (p = 85%) and deviant pairs (p = 15%), delivered in a random order. Standard and deviant tone pairs differed only in the direction of within-pair frequency change. In addition, the frequency levels of both the standard and deviant pairs varied randomly within a wide range in a block; thus the standard pairs shared the direction of the within-pair frequency change but not the absolute frequency level. Correspondingly, the deviant pairs only shared the opposite direction of the within-pair change. Nevertheless, the deviant tone pairs elicited MMN, implying that even the direction of the within-pair frequency change of the standard stimuli, and not just their absolute frequencies, developed a neural representation.

Acoustic Stimulation↗
PubMed1991

The speed of attentional shifts in the visual field.

The scanning speed of focal visual attention was measured directly by flashing a sequence of two, three, or four numerals one by one at random retinal positions and at a distance from each other to avoid interference between the numerals. Each numeral was followed by a mask pattern so the observers had to move their focal attention in the visual field in synchrony and at the same speed as the presentation rate of the numerals in order to recognize every numeral in the stimulus sequence. Observers could recognize the numerals orders of magnitude above the theoretical chance level of performance even when the presentation rate was as fast as 33 ms per numeral. However, the temporal order of the numerals was perceived rather poorly at the fast presentation rates and for the sequences of four numerals.

Attention↗
PubMed1989

Analysis of spatial structure in eccentric vision.

The analysis of spatial structure, ie, the encoding of relative positions between pattern elements, was studied in central and eccentric vision. In a two-alternative forced-choice task the observer had to discriminate between two patterns consisting of short line segments. At each trial the two patterns were flashed for 140 msec and the observer indicated whether the patterns were identical or mirror symmetric. Psychometric functions were measured by changing pattern size at each eccentricity in order to find the threshold size allowing 75% of correct responses. The scaling factor, required for discriminating between mirror symmetric and identical patterns independent of eccentricity, was found to be similar to the size-scaling proposed by Levi et al (Vision Res 25:963, 1985) for vernier acuity tasks.

Differential Threshold↗