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Biomedical subjects

S Frey

Publications and source records attributed to S Frey.

At least 37 records · Page 2Linked to original sources
PubMed2000

Structural and functional definition of the human chitinase chitin-binding domain.

Mammalian chitinase, a chitinolytic enzyme expressed by macrophages, has been detected in atherosclerotic plaques and is elevated in blood and tissues of guinea pigs infected with Aspergillus. Its normal physiological function is unknown. To understand how the enzyme interacts with its substrate, we have characterized the chitin-binding domain. The C-terminal 49 amino acids make up the minimal sequence required for chitin binding activity. The absence of this domain does not affect the ability of the enzyme to hydrolyze the soluble substrate, triacetylchitotriose, but abolishes hydrolysis of insoluble chitin. Within the minimal chitin-binding domain are six cysteines; mutation of any one of these to serine results in complete loss of chitin binding activity. Analysis of purified recombinant chitin-binding domain revealed the presence of three disulfide linkages. The recombinant domain binds specifically to chitin but does not bind chitosan, cellulose, xylan, beta-1, 3-glucan, beta-1,3-1,4-glucan, or mannan. Fluorescently tagged chitin-binding domain was used to demonstrate chitin-specific binding to Saccharomyces cerevisiae, Candida albicans, Mucor rouxii, and Neurospora crassa. These experiments define structural features of the minimal domain of human chitinase required for both specifically binding to and hydrolyzing insoluble chitin and demonstrate relevant binding within the context of the fungal cell wall.

Amino Acid Sequence↗
PubMed2000

Orbitofrontal involvement in the processing of unpleasant auditory information.

Although little is known about the contribution of the orbitofrontal cortex to the processing of new information in man, lesion studies in monkeys have suggested that it plays a critical role. The present study investigated changes in cerebral blood flow with positron emission tomography in normal human subjects during exposure to unpleasant auditory stimuli. The results indicated that the caudal orbitofrontal cortex, area 13, which is powerfully linked to the medial temporal limbic region and is involved in the regulation of autonomic responses, is a key part of the frontal cortex responding in the face of unpleasant incoming information.

Acoustic Stimulation↗
PubMed2000

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Journal Article↗
PubMed2000

Suppression of apoptosis in C3H mouse liver tumors by activated Ha-ras oncogene.

Liver tumors were induced in male C3H mice by a single injection of N-nitrosodiethylamine and characterized with respect to the presence of base substitutions in the hot-spot position at codon 61 of the Ha-ras proto-oncogene. An increase in Ha-ras mutation prevalence was found with time after induction of tumors, suggesting that the activated ras gene provides a selective growth advantage. However, no significant differences in 5-bromodeoxyuridine labeling indices were evident between ras mutated and ras wild-type tumors, demonstrating that cell division rates in the two tumor populations were very similar. Apoptotic indices were determined by counting eosinophilic apoptotic bodies. The frequency of occurrence of apoptotic bodies was found to be approximately five times lower in tumors with Ha-ras mutations when compared with tumors not showing the mutation. This demonstrates that the activated p21(Ras) protein has anti-apoptotic activity in transformed mouse hepatocytes in vivo and suggests that the preferential outgrowth of Ha-ras-mutated hepatoma cells is mediated by suppression of apoptosis rather than by stimulation of cell division.

Animals↗
PubMed1999

[Mobilizing or stabilizing exercise in degenerative disk disease in the lumbar region?].

Degenerative disc disease may affect younger and middle-aged people with a kind of premature disc degeneration. The majority of these low back pain patients are not candidates for a spinal fusion and are in need of a structured conservative treatment. In a controlled clinical trial, 27 low back pain patients (mean age 40 years, range 25-48) with a mean duration of symptoms of 7.4 years, were randomized to mobilizing (n = 12) or stabilizing (n = 15) daily half hour exercise for an eight weeks period. A clinical overall score (COS) based on pain intensity (VAS), physical signs, functional status (Oswestry) and analgetics was used as outcome criterion. The treatment results were best for the group undergoing stabilizing treatment. They achieved a 17% reduction in COS, compared to a 10% increase in the group undergoing mobilizing treatment (p = 0.02). These types of exercises are discussed in relation to the instability theory in disc degeneration.

Adult↗
PubMed1999

Human cortical gustatory areas: a review of functional neuroimaging data.

In an effort to define human cortical gustatory areas we reviewed functional neuroimaging data for which coordinates standardized in Talairach proportional space were available. We observed a wide distribution of peaks within the insula and parietal and frontal opercula, suggesting multiple gustatory regions within this cortical area. Multiple peaks also emerged in the orbitofrontal cortex. However, only two peaks, both in the right hemisphere, were observed in the caudolateral orbitofrontal cortex, the region likely homologous to the secondary taste area described in monkeys. Overall significantly more peaks originated from the right hemisphere suggesting asymmetrical cortical representation of taste favoring the right hemisphere.

Brain Mapping↗
PubMed1999

Visceral protein status and caloric intake in exercising versus nonexercising individuals with end-stage renal disease.

OBJECTIVE: To determine if differences exist in kilocalorie and protein intake and visceral protein levels for patients with End-Stage Renal Disease (ESRD) exercising during dialysis versus not exercising. DESIGN: Prospective study of 11 patients with ESRD over a study period of 12 weeks. SETTING: Outpatient renal dialysis clinic. PATIENTS: Patients with ESRD undergoing hemodialysis (HD) three times weekly who met the following criteria were selected: aged 25 to 65 years, nondiabetic, no current physical activity, blood pressure of 160/95 mm Hg or less at the second hour of HD, no unstable angina pectoris. Eleven patients who met the criteria were randomized into two groups; five patients with exercise (E) and six patients without exercise (NE). INTERVENTIONS: From weeks 5 to 8, E patients began exercise during HD three times a week. Exercise gradually increased by 3 minutes each dialysis day, maintaining 60% to 80% maximal heart rate (HR). By the end of week 8, all E patients reached 45 minutes of exercise, including 5 minutes each of warm-up and cooldown. Patients continued 45 minutes of exercise each dialysis day during HD at 60% to 80% maximal HR during weeks 9 through 12. NE patients remained sedentary throughout the study. MAIN OUTCOME MEASURE: Twenty-four-hour dietary recalls were obtained weekly for the 12 weeks from all patients for kilocalorie and protein intake. Serum levels of prealbumin, transferrin, and predialysis and postdialysis albumin were obtained immediately before the study onset and at weeks 4, 8, and 12. Comments related to patients' feelings and exercise were recorded but not analyzed statistically. RESULTS: Analysis of covariance for repeated measures for kilocalories yielded no significance by group or over time. Mean intakes for E patients for weeks 9 through 12 were clinically greater than weeks 1 through 8 by approximately 200 kilocalories. The mean protein intake for E patients at weeks 9 through 12 (79 +/- 41 g) appeared clinically greater than NE patients at weeks 9 through 12 (58 +/- 11 g), although not statistically different. Adequacy of dialysis (Kt/V) and initial levels of each serum protein were covariates for analysis of variance. No statistical differences were found for prealbumin levels. Transferrin levels were within normal ranges but differed (P <.05) by group (E or NE) and time periods. Prealbumin and postalbumin concentrations ranged from slightly low to adequate levels and were different over time (P <. 05). CONCLUSION: Kilocalorie and protein intakes appeared to increase for E patients during the exercise program. No consistent increases of visceral proteins were found for E patients. A majority of E patients expressed feelings of improved health, better exercise tolerance, and improved appetite and viewed exercise as enjoyable.

Adult↗
PubMed1999

Ibotenic acid lesions of the basolateral, but not the central, amygdala interfere with conditioned taste aversion: evidence from a combined behavioral and anatomical tract-tracing investigation.

Rats (Rattus norvegicus) with almost complete ibotenic acid lesions (at least 90%) of the basolateral amygdaloid complex (BLA) failed to learn a conditioned taste aversion (CTA; Experiment 1A). In these same BLA rats, the bidirectional parabrachial-insular pathway that courses through the central nucleus of the amygdala (Ce) was shown to be spared (Experiment 1B), indicating that the BLA per se is critical for CTA learning. In contrast to the deleterious effect of BLA lesions on CTA, ibotenic acid lesions of the Ce did not block CTA learning (Experiment 2). Nonreinforced preexposure to the gustatory stimulus attenuated CTA acquisition in normal rats, and, under these conditions, rats with BLA lesions were no longer impaired (Experiment 3). Thus, ibotenic acid lesions centered over the Ce, sparing a considerable extent of the BLA, together with the testing procedure used in previous experiments (e.g., L. T. Dunn & B. J. Everitt, 1988), led to the belief that the CTA deficits reported after electrolytic lesions of the amygdala were the result of incidental damage to fibers of passage.

Amygdala↗
PubMed1999

Re-examination of the human taste region: a positron emission tomography study.

There is considerable uncertainty regarding the cortical areas in the human brain that are involved in gustatory processing. Evidence from nonhuman primates indicates that parts of the peri-central opercular region (secondary somatosensory cortex) and insular cortex may be important for gustatory processing. The aim of the study was to examine changes in cerebral blood flow during gustatory stimulation (with sucrose or water) in the insulo-opercular region of the human brain with positron emission tomography using only movement of the tongue and mouth as control conditions. This is important because subtractions of responses to one gustatory stimulus from those to another may mask gustatory activity that is common to both stimuli, even when the control stimulus is an apparently tasteless one (e.g. water). Bilateral increases in activity were observed in the insulo-opercular region and, consistent with animal work, they indicate that there are a number of separate foci within this general area where primary gustatory inputs may be processed.

Adult↗
PubMed1999

Interference of antibody production to hepatitis B surface antigen in a combination hepatitis A/hepatitis B vaccine.

A randomized trial comparing 3 manufacturing consistency lots of a combination hepatitis A/hepatitis B vaccine to each other and to hepatitis A vaccine and hepatitis B vaccine given separately and concurrently was done to evaluate safety, tolerability, and immunogenicity. Healthy volunteers >/=11 years of age were divided into 4 groups. Each of 3 groups received a separate consistency lot of the combination vaccine, and 1 group received separate but concurrent injections of hepatitis A and hepatitis B vaccines. Injections were given at weeks 0 and 24. The combination vaccine was generally well tolerated. The hepatitis A portion of the combination vaccine produced clinically acceptable high seropositivity rates 4 and 52 weeks after the first injection. The hepatitis B portion of the vaccine did not produce clinically acceptable seropositivity rates 4 weeks after the second injection. Lack of antibody production may be attributed, at least in part, to immunologic interference.

Adolescent↗
PubMed1998

Mismatch repair deficiency interferes with the accumulation of mutations in chronically stimulated B cells and not with the hypermutation process.

Primary responses to the hapten phenyloxazolone and chronic responses to environmental antigens occurring in Peyer's patches were analyzed in two different mismatch repair-deficient backgrounds. Paradoxically, whereas primary responses were found normal in MSH2- and only slightly diminished in PMS2-deficient mice, mutations in Peyer's patch B cells from both k.o. animals were reduced three times, the subset of Peyer's patch B cells with highly mutated sequences being specifically missing in the mismatch repair-deficient context. Strikingly, germinal center B cells from Peyer's patches of k.o. animals showed microsatellite instability at an unprecedented level. We thus propose that the amount of DNA damages generated prevents these cells from recycling in germinal centers and that mismatch repair deficiency is only the indirect cause of the lower mutation incidence observed.

Adenosine Triphosphatases↗
PubMed1998

A dose response study of hepatitis A vaccine in healthy adults who are > or = 30 years old and weigh > or = 77 kg.

The dose response relationship of 25-, 50-, and 100-U doses of an inactivated hepatitis A vaccine was examined in 358-seronegative volunteers in a 2-dose schedule. The 50-U and 100-U groups had statistically significantly higher seroconversion rates than the 25-U group at weeks 2, 4, 8, and 24. Seroconversion was statistically significantly greater for the 100-U compared with the 25- and 50-U doses 2 weeks after the first injection but was not significantly different by 4 weeks after the first injection in the 50- and 100-U dose groups. After 2 injections, all subjects in all groups seroconverted. The vaccine was well tolerated at all dosage levels.

Adult↗
PubMed1997

A neuroanatomical method to assess the integrity of fibers of passage following ibotenate-induced damage to the central nervous system.

In some behavioral-lesion experiments involving animals, ibotenic acid (IBO) is used as a means of damaging brain structures. Occasionally one needs to assess the status of fibers coursing through the damaged area to determine whether the deficits observed are the result of destruction of neurons rather than fibers. In such cases, IBO, is considered to be the method of choice since it destroys cell bodies but leaves fibers of passage intact. However, if the IBO dose injected in a given area is too high, both cell bodies and fibers of passage could be damaged. The anterograde and retrograde tracer wheat germ agglutinin-horseradish peroxidase (WGA-HRP) is a useful technique to verify that fibers are intact, and is a more powerful tool in comparison with a tracer, such as HRP, which has been used in previous studies.

Amygdala↗
PubMed1996

Evidence for the existence of both proteasomes and a novel high molecular weight peptidase in Entamoeba histolytica.

To screen for high molecular weight proteases in Entamoeba histolytica, we subjected a soluble amebal extract to density gradient centrifugation and tested the fractions for activity against the chymotryptic peptide substrate, Suc-leucyl-leucyl-valyl-tyrosyl-4-methylcoumaryl-7-amide. Two peaks of activity, of approximately 11 and 20 S, were clearly separated. Based on SDS-electrophoretic pattern and immunoblot analysis, we ascribe the 20 S activity to proteasomes. The 11 S protein was purified from amebal homogenates by a series of chromatographic steps. As determined by molecular sieve chromatography and nondenaturing gel electrophoresis, the native complex had an apparent Mr of 385,000 +/- 10%. On SDS gels, the purified enzyme exhibited a single band of Mr 62,000 that yielded a single N-terminal sequence, indicating that the preparation was homogeneous and that the native complex consisted of six very similar or identical subunits. The enzyme preferred peptides with aromatic residues at the P1 position and had low but distinct activity toward azocasein. We conclude that the 11 S enzyme is a novel high molecular weight protease that is distinct from proteasomes.

Amino Acid Sequence↗
PubMed1996

Influence of actinomycin D, a RNA synthesis inhibitor, on long-term potentiation in rat hippocampal neurons in vivo and in vitro.

1. Hippocampal long-term potentiation (LTP) may serve as an elementary process underlying certain forms of learning and memory in vertebrates. As is the case with behavioural memory, hippocampal LTP in the rat CA1 region and in the dentate gyrus occurs in stages, which can be separated by an inhibitor of RNA synthesis. 2. Experiments have been performed in two brain regions, in the hippocampal CA1 region in vitro and in the dentate gyrus in vivo. 3. Maintenance of hippocampal LTP in the CA1 region in vitro was influenced by the RNA synthesis inhibitor actinomycin D from 4 h onwards. 4. The effect of actinomycin D on the time course of the population spike potentiation was more pronounced than the effect on the time course of the EPSP component, suggesting different mechanisms for the two forms of potentiation. 5. Intrahippocampal and intracerebroventricular injection of actinomycin D into rats prevented a late stage of LTP in the dentate gyrus in vivo measured as the population spike amplitude. 6. Since actinomycin D was only effective in influencing the maintenance of LTP when applied before tetanization, the requirement for transcription during LTP may have a critical time window. 7. Actinomycin D influenced the maintenance of LTP specifically, since the drug did not alter any potentials in control experiments after its removal or when it was administered shortly after tetanization. A second, structurally different RNA synthesis inhibitor, 5,6-dichloro-1-beta-D-ribofuranosyl benzimidazole, mimicked the effect of actinomycin D in vitro.

Animals↗
PubMed1996

Perception of motion-in-depth in patients with partial or complete cerebral hemispherectomy.

Four patients with functional hemispherectomy, one patient with a complete anatomical hemispherectomy, and one patient with unilateral removal of the temporal, parietal and occipital lobes took part in two sets of experiments designed to investigate their residual sensitivity to motion-in-depth in the hemianopic visual field. Two types of computer-generated visual displays were used; in the first set of experiments, a dot pattern and in the second, a circular checkerboard. These simulated either convergent, divergent or reversed rotational motion. Each set of experiments consisted of two parts; in the first part, electrodermal responses were monitored during stimulus presentation while the subjects performed a simple distracting task. In the second part, subjects were asked to state verbally the direction of stimulus motion. Contrary to expectations, no reliable changes in skin conductance were elicited from any of the subjects by changes in the direction of motion of the component parts of either the dot pattern display or the circular checkerboard display. Furthermore, none of the subjects were able to discriminate the direction of motion of the target patterns when presented in the hemianopic field. The most parsimonious explanation is that the subcortical visual pathways which survive hemispherectomy are unable to process visual information relating to motion in depth.

Adolescent↗