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Biomedical subjects

T Carlson

Publications and source records attributed to T Carlson.

At least 19 recordsLinked to original sources

Evaluation of the toxicity of concentrated barley beta-glucan in a 28-day feeding study in Wistar rats.

Beta-glucans are water-soluble cell-wall polysaccharides consisting of (1-->3,1-->4)-linked beta-D-glucopyranosyl monomers that comprise a considerable proportion of soluble fiber from certain grains including oats and barley. Consumption of foods containing beta-glucan or beta-glucan-enriched fractions prepared from these grains lower serum cholesterol concentrations in humans and in animal models of hypercholesterolemia. The present study was conducted to evaluate the toxicity of beta-glucan-enriched soluble fiber from barley in Wistar rats on dietary administration at concentrations of 0.7, 3.5 and 7% beta-glucan for 28 days. There were no adverse effects on general condition and behavior, growth, feed and water consumption, feed conversion efficiency, red blood cell and clotting potential parameters, clinical chemistry values, and organ weights. Necropsy and histopathology findings revealed no treatment-related changes in any organ evaluated. A dose-dependent increase in full and empty cecum weight was observed. This is a common physiological response of rodents to high amounts of poorly digestible, fermentable carbohydrates, and was of no toxicological concern. The only finding of possible biological relevance was an increase in the number of circulating lymphocytes observed in males. However, the increase was not dose-dependent and was not observed in females. Results of this study demonstrated that consumption of concentrated barley beta-glucan was not associated with any obvious signs of toxicity in Wistar rats even following consumption of large quantities.

Animal Feed↗

Complex regulation of the yeast heat shock transcription factor.

The yeast heat shock transcription factor (HSF) is regulated by posttranslational modification. Heat and superoxide can induce the conformational change associated with the heat shock response. Interaction between HSF and the chaperone hsp70 is also thought to play a role in HSF regulation. Here, we show that the Ssb1/2p member of the hsp70 family can form a stable, ATP-sensitive complex with HSF-a surprising finding because Ssb1/2p is not induced by heat shock. Phosphorylation and the assembly of HSF into larger, ATP-sensitive complexes both occur when HSF activity decreases, whether during adaptation to a raised temperature or during growth at low glucose concentrations. These larger HSF complexes also form during recovery from heat shock. However, if HSF is assembled into ATP-sensitive complexes (during growth at a low glucose concentration), heat shock does not stimulate the dissociation of the complexes. Nor does induction of the conformational change induce their dissociation. Modulation of the in vivo concentrations of the SSA and SSB proteins by deletion or overexpression affects HSF activity in a manner that is consistent with these findings and suggests the model that the SSA and SSB proteins perform distinct roles in the regulation of HSF activity.

DNA-Binding Proteins↗

The yeast heat shock transcription factor changes conformation in response to superoxide and temperature.

In vitro DNA-binding assays demonstrate that the heat shock transcription factor (HSF) from the yeast Saccharomyces cerevisiae can adopt an altered conformation when stressed. This conformation, reflected in a change in electrophoretic mobility, requires that two HSF trimers be bound to DNA. Single trimers do not show this change, which appears to represent an alteration in the cooperative interactions between trimers. HSF isolated from stressed cells displays a higher propensity to adopt this altered conformation. Purified HSF can be stimulated in vitro to undergo the conformational change by elevating the temperature or by exposing HSF to superoxide anion. Mutational analysis maps a region critical for this conformational change to the flexible loop between the minimal DNA-binding domain and the flexible linker that joins the DNA-binding domain to the trimerization domain. The significance of these findings is discussed in the context of the induction of the heat shock response by ischemic stroke, hypoxia, and recovery from anoxia, all known to stimulate the production of superoxide.

Amino Acid Sequence↗

Single polyprenol and dolichol isolation by semipreparative high-performance liquid chromatography technique.

A new method of separation of single polyprenols (or dolichols) from a mixture of isoprenoid alcohols is described. Application of a high-performance liquid chromatography (HPLC) apparatus equipped with a semipreparative ODS column resulted in preparation of long-chain (dihydro)polyprenols of high purity (>95%). This approach substantially decreases the time scale of the conventional chromatographical preparative procedure. The method can be widely used in chemical and biochemical projects, where single polyprenols or dolichols are required.

Chromatography, High Pressure Liquid↗

A novel plant-derived inhibitor of cAMP-mediated fluid and chloride secretion.

We have identified an agent (SP-303) that shows efficacy against in vivo cholera toxin-induced fluid secretion and in vitro cAMP-mediated Cl- secretion. Administration of cholera toxin to adult mice results in an increase in fluid accumulation (FA) in the small intestine (FA ratio = 0.63 vs. 1.86 in control vs. cholera toxin-treated animals, respectively). This elevation in FA induced by cholera toxin was significantly reduced (FA ratio = 0.70) in animals treated with a 100 mg/kg dose of SP-303 at the same time as the cholera treatment. Moreover, when SP-303 was administered 3 h after cholera toxin, a dose-dependent inhibition of FA levels was observed with a half-maximal inhibitory dose of 10 mg/kg. In Ussing chamber studies of Caco-2 or T84 monolayer preparations, SP-303 had a significant effect on both basal current and forskolin-stimulated Cl- current. SP-303 also induced an increase in resistance that paralleled the observed decrease in current. These data suggest that SP-303 has an inhibitory effect on cAMP-mediated Cl- and fluid secretion. Thus SP-303 may prove to be a useful broad-spectrum antidiarrheal agent.

Animals↗

A role for RNA metabolism in inducing the heat shock response.

Yeast HSF is constitutively trimeric and DNA bound. Heat shock is thought to activate HSF by inducing a conformational change. We have developed an assay in which we can follow a conformational change of HSF that correlates with activity and thus appears to be the active conformation. This conformational change requires two HSF trimers bound cooperatively to DNA. The conformational change can be induced in whole cell extracts, and is thus amenable to biochemical analysis. We have purified a factor that triggers the conformational change. The factor is sensitive to dialysis, insensitive to NEM, and is not extractable by phenol. It is small, and apparently not a peptide. Mass spectroscopy identifies a novel guanine nucleotide that tracks with activity on columns. This novel nucleotide, purchased from Sigma, induces the conformational change (although this does not prove the identity of the activating factor unambiguously, because Sigma's preparation is contaminated with other compounds). What is the source of this nucleotide in cells? Activity can be generated by treating extracts with ribonuclease; this implicates RNA degradation as a source of HSF-activating activity. The heat shock response is primarily responsible for monitoring the levels of protein chaperones; how can RNA degradation be involved? Synthetic lethal interactions link HSF activity to ribosome biogenesis, suggesting a possible model. Ribosomal proteins are produced in large quantities, and in excess of rRNA; unassembled r-proteins are rapidly degraded (t1/2 approximately 3 min). Unassembled r-proteins aggregate readily. It is likely that unassembled r-proteins represent a major target of chaperones in vivo, and for proteasome-dependent degradation. Interference with rRNA processing (e.g., by heat shock) requires hsp70s to handle the aggregation-prone r-proteins, and proteasome proteins to help degrade the unassembled r-proteins before they aggregate. A nucleotide signal could be generated from the degradation products of the rRNA itself.

DNA↗

Mycobacterium bovis in coyotes from Michigan.

During a survey for tuberculosis in wild carnivores and omnivores, Mycobacterium bovis was cultured from pooled lymph nodes of three adult female coyotes (Canis latrans) harvested by hunters in Michigan (USA). No gross or histologic lesions suggestive of tuberculosis were seen in these animals. One coyote was taken from Montmorency county and two coyotes from Alcona county located in the north-eastern portion of Michigan's Lower Peninsula where free-ranging white-tailed deer (Odocoileus virginianus) have been found infected with bovine tuberculosis. It is thought that these coyotes became infected with M. bovis through the consumption of tuberculous deer. Other species included in the survey were the opossum (Didelphis virginiana), raccoon (Procyon lotor), red fox (Vulpes vulpes), bobcat (Felis rufus), and badger (Taxidea taxus).

Animal Feed↗

Bovine tuberculosis in free-ranging white-tailed deer from Michigan.

A 4.5 yr-old male white-tailed deer (Odocoileus virginianus) killed by a hunter during the 1994 firearm hunting season in northeastern Michigan (USA) had lesions suggestive of tuberculosis and was positive on culture for Mycobacterium bovis the causative agent for bovine tuberculosis. Subsequently, a survey of 354 hunter-harvested white-tailed deer for tuberculosis was conducted in this area from 15 November 1995 through 5 January 1996. Heads and/or lungs from deer were examined grossly and microscopically for lesions suggestive of bovine tuberculosis. Gross lesions suggestive of tuberculosis were seen in 15 deer. Tissues from 16 deer had acid-fast bacilli on histological examination and in 12 cases mycobacterial isolates from lymph nodes and/or lungs were identified as M. bovis. In addition, lymph nodes from 12 deer (11 females and 1 male) without gross or microscopic lesions were pooled into 1 sample from which M. bovis was cultured. Although more male (9) than female (3) deer had bovine tuberculosis infections, this difference was not statistically significant. Mycobacterium bovis culture positive deer ranged in age from 1.5 to 5.5 yr with a mean of 2.7 yr (median 2.5 yr) for males and 3.2 yr (median 3.5 yr) for females. This appears to be the first epidemic occurrence of M. bovis in free-ranging cervids in North America. A combination of environmental (high deer density and poor quality habit) and management-related factors (extensive supplemental feeding) may be responsible for this epizootic.

Animals↗

The economic impact on families of children's participation in junior sport.

The study investigated the socio-economic consequences for families of participation in junior sport. Two hundred and twenty families in Queensland and Victoria were surveyed from the sports of cricket, Australian football, gymnastics, hockey, netball and tennis and twenty seven of these interviewed. The study showed that parents make a substantial contribution in terms of financial support to their children's participation in junior sport. Each of the sports mode different financial demands on families depending on the yearly cycle of training and competition, distance from facilities and coaching, costs associated with coaching, equipment and uniforms, and representative level. It is concluded that family income and structure are the key factors in determining the likelihood of a child's involvement in junior sport, and that for many Australian children, financial factors may be barriers to their participation in junior sport.

Adolescent↗

Longevity of glass-ionomer restorative materials: results of a 10-year evaluation.

Three restorative materials used for cervical erosion /abrasion lesions were evaluated clinically after 10 years. Thirty adult patients with at least four cervical lesions received one restoration of each of Ketac-Fil, finished immediately, Ketac-Fil, finished after a delay, Chelon-FIl (all glass-ionomer cements), and Cervident (a resin composite). Restorations were placed without any tooth preparations. Eighteen patients returned for their 10-year examinations. Two experienced examiners provided the periodic evaluations. Complete retention at 10 years was 83% for Ketac-Fil, finished immediately; 78% for Ketac-Fil, finished after a delay; 67% for Chelon-Fil; and 17% for Cervident. All three glass-ionomer restorative materials exhibited statistically significantly greater retention that did Cervident. When a noninvasive procedure is desired, glass-ionomer materials are the restorative material of choice for abrasion/erosion lesions because of their long-term retention values.

Adult↗

Efficacy of a topical nasal decongestant in different formulations: the effect of viscosity.

Factors affecting the absorption of drugs through the nasal mucosa are increasingly being studied. Dosage form factors, i.e. the viscosity of the excipients, have been claimed to be of importance for enhanced nasal absorption due to prolongation of contact time between drug and mucosa. In the present study, a comparison was made of the effect of a local nasal sympathomimetic when administered intranasally in formulations with different viscosities. Volunteers received the test drugs as nasal sprays in a randomized cross-over design by a rhinomanometric technique, the effect of the drug being recorded for up to 5 h after administration. No significant differences in effects were observed when the test formulations were compared.

Absorption↗

Listening preferences for voice types as a function of age.

This experiment was designed primarily to generate information about the preferences of older listeners for various classes of voices. Speech samples for that purpose were elicited from 80 speakers, who provided the desired stimuli (sentences) under frequency and intensity control. Specifically, there were eight cells in the design, each represented by 10 speakers (5 male and 5 female); all combinations of low, medium, and high speaker fundamental frequency (SFF) were combined with soft, middle and loud vocal intensity (VI) productions--except for the low-SFF/high-VI combination, which proved impossible to obtain. Listeners were four groups of 20 individuals equally divided as to sex. The two older of these groups, designated as the experimental subjects, were: older adults (60-70 years of age) and the elderly (80-90 years). The two younger groups served as controls; they included young adults (20-30 years of age) and middle-aged adults (aged 40-50 years). Listeners rated each speech sample on a 5-point preference scale varying from "like very much" to "dislike very much." The results suggest that most listeners prefer medium intensity voices. Other preference tendencies were toward low-pitched voices and (slightly) toward male speakers; but these trends were not as marked as the first. Most importantly, there were no systematic differences in voice type preferences between or among the older and younger groups--or between male and female listeners.

Adult↗

Nesidioblastosis in an adult: an illustrative case and collective review.

Nesidioblastosis is a term that describes multifocal hyperplasia of all pancreatic cell components and is characterized primarily by their disorganization and proliferation throughout the entire pancreas. This condition is the most common cause of persistent neonatal hypoglycemia. Since it is so exceedingly rare in adults no consensus regarding its surgical management is available. Our patient underwent celiotomy with a presumptive diagnosis of insulinoma. No adenoma was found and frozen sections suggested hyperplasia. Even when Whipple's triad is met and all biochemical and roentgenographic analyses suggest insulinoma, another etiology may be the cause. Intraoperative ultrasonography may aid in the diagnosis especially after a negative exploration. The diagnosis of nesidioblastosis can be confirmed by frozen section especially if adenomatosis is present. The degree of resection required is problematic because no large series exists. This case is presented with special emphasis given to etiology, pathology, preoperative work-up, and operative strategy.

Blood Chemical Analysis↗

Further studies of the turnover of dog antithrombin III. Study of 131I-labelled antithrombin protease complexes.

Fresh plasma containing 131I-antithrombin III (*I-AT) was coagulated and incubated at 37 degrees C for 2 hr. A "complex peak," separated on heparin-agarose contained AT and *I-AT antigen but no heparin cofactor activity. Crossed immunoelectrophoresis showed only AT complexes. SDS PAGE showed 80% of the *I-AT in a major band (approximately 80,000 daltons), 15% in a minor band (approximately 100,000 daltons) and the rest in trace bands (approximately 60,000 and/or 115,000 daltons). Ammonia treatment of the complex peak released alpha-thrombin. After i.v. injection 80% of the complexed *I-AT, chiefly as the major band, left the plasma with t 1/2 approximately 15 min and was almost immediately catabolized to low molecular weight breakdown products. A major catabolic site was the liver. A simple kinetic model describes the findings approximately.

Animals↗