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Biomedical subjects

S M Specht

Publications and source records attributed to S M Specht.

15 recordsLinked to original sources
PubMed2000

Inhibition of the allograft response by donor specific blood transfusion: association with reduced local TH1 cytokines and nitric oxide but enhanced prostaglandin E2 production.

BACKGROUND: Donor-specific blood transfusion (DST) may improve allograft survival in human and animal models, but the mechanisms for this graft protective effect are incompletely understood. The sponge matrix allograft model was used to determine if DST induces regulatory factors within the allograft. METHODS: C57BL/6 (H-2b) recipients received donor-specific (DBA/2J, H-2d) or syngeneic (C57BL/6) blood 7 days before sponge matrix allograft (DBA/2J) implantation. Fourteen days postgrafting, the sponge infiltrating cells (SIC) were examined for cytotoxic T cell (CTL) and natural killer (NK) activity, and sponge exudate fluid (SEF) was assessed for nitric oxide (.N=O) and prostaglandin E2 (PGE2) content. Interleukin- (IL) 2, IL-4, IL-10, and interferon-gamma (IFN-gamma) production by SIC was also determined. Recipient splenocytes were simultaneously assessed for anti-donor cytotoxic and proliferative responses and .N=O production. RESULTS: SIC from mice receiving syngeneic transfusions (ST) acquired both CTL and NK activity postgrafting, with maximal activity by day 14. DST suppressed both CTL and NK activity throughout the postgrafting period. Limiting dilution analysis (LDA) of SIC to determine precursor and native CTL frequency showed significantly lower responder cell frequency after DST compared with ST. SEF .N=O levels and SIC production of IL-2 and IFN-gamma in grafted DST mice were significantly lower than in grafted mice receiving ST. No significant amounts of IL-4 and very low levels of IL-10 were produced by SIC from grafted mice after either ST or DST. Conversely, PGE2 content of sponge fluid and serum from DST mice was higher than in mice receiving ST. Antigen stimulated splenocyte proliferation and CTL development assessed by LDA were also inhibited by DST. CONCLUSIONS: Reduction in local TH1 cytokines, absence of detectable TH2 cytokines, with enhanced PGE2 and depressed .N=O were observed in the local graft environment after DST. These data support the hypothesis that DST induces donor-specific intragraft suppressor factors, accompanied by reduced local and systemic immune activation.

Animals↗
PubMed2000

Graft hyporeactivity induced by immature donor-derived dendritic cells.

Immature dendritic cells (DCs) are deficient in surface co-stimulatory molecules and have been shown to exhibit a 'tolerogenic' potential. We investigated the allostimulatory activity of immature DCs in one-way mixed leukocyte reactions and their capacity to inhibit anti-donor cytolytic activity in the sponge matrix allograft model. Immature DCs (CD80 and CD86 deficient) were derived from bone marrow cells propagated in GM-CSF and TGF-beta1. Mature DCs (CD80+ and CD86+) were derived from bone marrow cells propagated in GM-CSF and IL-4. Either 2 x 10(6) DBA/2J (DBA, H-2d) immature DCs or 2 x 10(6) mature DCs were injected intravenously into C57BL/6J (B6, H-2b) mice 7 days prior to sponge matrix allograft implantation. On day 12, the sponge was harvested and the graft-infiltrating cells were tested in vitro for cytotoxic T lymphocyte (CTL) activity. Immature dendritic cell (DC) infused significantly and markedly inhibited intra-graft CTL activity compared to mature DCs and syngeneic bone marrow control cells. The administration of immature DCs directly into the sponge allograft failed to induce hyporeactivity. Thus, the only systemic infusion of immature donor DCs was able to recapitulate the donor-specific transfusion effect, and the capacity of donor bone marrow cells to induce donor-specific hyporeactivity in the sponge allograft model.

Animals↗
PubMed1999

Human taste contrast and self-reported measures of anxiety.

Successive negative taste contrast in humans was demonstrated with a common taste stimulus, i.e., cherry-flavored Kool-Aid. A total of 31 male and female college-aged participants rated a 7% sucrose solution which was cherry-flavored as less sweet when it was preceded by a 28% rather than a 7% sucrose solution which was cherry-flavored. Because drugs such as the benzodiazepines affect taste contrast in rats and act as anxiolytics in humans, the present experiment also examined whether several self-reported measures of anxiety were related to taste contrast in humans. Neither scores on Taylor's Manifest Anxiety Survey nor those on the State-Trait Anxiety Inventory were related to "sweetness" ratings or contrast effects.

Analysis of Variance↗
PubMed1996

Behavioral components of milk-induced activation in neonatal rat pups.

Neonatal rat pups exhibit a complex constellation of behaviors in response to a variety of salient stimuli such as the odor of milk or maternal saliva, stroking with a soft brush, electrical brain stimulation, and intraoral infusions of milk. Although psychobiologists have used the term "behavioral activation" to refer to such behavioral displays, the exact nature of "behavioral activation" and its underlying neural substrates have yet to be elucidated. This study was undertaken to characterize "behavioral activation" quantitatively to describe and define this apparently global pattern of response in terms of possible underlying components. Principal components analysis suggested that "behavioral activation" may be comprised of separable ingestive, exploratory, and locomotor behavioral "assemblies."

Animals↗
PubMed1994

Carcass composition of "bob" and "special-fed" veal and its prediction.

Percentage of lean, fat, and bone were determined in 18 bob veal (BV) and 28 special-fed veal (SFV) carcasses. Carcasses were subjected to a set of visual conformation scores and a variety of physical measurements. No significant differences were found regarding carcass percentage of lean, fat, and bone within the three BV weight groups (P > .05). On average, SFV were 12% fatter than BV and did not have a greater percentage of lean (P > .05), except for SFV carcasses weighing 88.2 to 97.7 kg. Bob veal had less fat (internal, external, and intermuscular) and a higher bone percentage than SFV (P < .05). The round and shoulder primals had the greatest proportion of lean in both the BV and SFV carcasses. Bob veal carcasses had an average conformation score of average Good and SFV carcasses had an average conformation score of average Choice. In addition, a parsimonious subset of variables was identified for predicting total percentage of lean (TPLEAN) for both BV and SFV separately, using "stepwise" regression model building procedures. For BV, all four identified predictor variables were subjective conformation scores (i.e., muscling, appearance, leg thickness, loin-back plumpness) (R = .73, P < .03). For SFV, four predictor variables were also identified: kidney and pelvic fat, fat thickness, carcass length, and lateral thickness (R = .61, P < .03). Although both regression equations were significant predictors of TPLEAN, confidence limits for predicting future TPLEAN value were wide relative to the variation in the actual TPLEAN values. Thus, the practical utility of the regression equations is limited.

Adipose Tissue↗
PubMed1991

Energy utilization and organ mass of Targhee sheep selected for rate and efficiency of gain and receiving high and low planes of nutrition.

Two experiments were conducted to examine changes in usage of energy and visceral organ mass in Targhee lambs selected on the basis of improved rate and efficiency of growth. In Exp. 1, Targhee ram lambs from a breeding line selected for improved growth rate and feed efficiency and a control line that was maintained without selection for 20 yr were provided with either a high (ad libitum) or low (maintenance) plane of nutrition. Rams were slaughtered and weights of the visceral organs were recorded. Analysis of variance, using a factorial model with BW as a covariant, was used to examine effects of lines of breeding, plane of nutrition, interaction between line of breeding and plane of nutrition, and days on feed. Weights of liver, kidneys, rumen, abomasum, and small and large intestines from lambs receiving a high plane of nutrition were, respectively, 39, 25, 12, 28, 40, and 31% greater than weights of those tissues in lambs receiving a low plane of nutrition. Ruminal weights were 13% greater for rams from the select line of breeding than for those from the control line. In Exp. 2, seven Targhee ewe lambs from the select line and eight from the control line were examined for differences in heat production and energy usage by indirect open circuit respiration calorimetry using a completely randomized design. Fasting heat production of lambs from the select line was 7.8% greater than that of lambs from the control line. Partial efficiencies of ME used for maintenance and tissue accretion were not different between lines of breeding.(ABSTRACT TRUNCATED AT 250 WORDS)

Animal Nutritional Physiological Phenomena↗
PubMed1990

Injection of 5,7-dihydroxytryptamine into the B3 raphe region of neonatal rat pups induces hyperalgesia but only slight alterations in ingestion-related behaviors.

The effects of intrabrainstem injections of the neurotoxin 5,7-dihydroxytryptamine (5,7-DHT) into the B3 raphe region (nucleus raphe magnus and nucleus reticularis paragigantocellularis) on early ingestive behavior and nociception were assessed in Sprague-Dawley rat pups during the first postnatal week. Lesions resulted in a marked depletion of serotonin (5HT) in hindbrain without influencing 5HT levels in forebrain. Pretreatment with desipramine (DMI) resulted in a sparing of noradrenergic neurons from neurotoxic effects. The B3 lesion resulted in significant hyperalgesia as reflected by decreased latencies in tail flick testing. Although nipple attachment latencies in suckling tests were slightly increased by the lesion, no notable effects on mouthing or other ingestive-related behaviors were observed in testing conducted in an independent ingestion paradigm. These results suggest that whereas B3 serotonergic neurons may be functioning in an adult-typical manner to regulate analgesia during the early postnatal period, this raphe region may play only a slight role in the modulation of ingestion-related behaviors early in life.

5,7-Dihydroxytryptamine↗
PubMed1990

Effect of phosphate buffer agar on the number of UV-induced mutations to streptomycin resistance in Escherichia coli strains.

The number of UV-induced mutations to streptomycin resistance in Escherichia coli B/r cells depends on the post-irradiation incubation medium. When cells are incubated on phosphate buffer agar (PBA) as opposed to brain heart infusion agar (BHI), there is an irreversible loss in the number of potential streptomycin resistant mutants which develop. This decrease in mutant numbers is known to occur without a corresponding loss in overall cell viability and cannot be explained in terms of the kinetics of dimer excision. Recent studies have indicated that pyrimidine dimers are the substrate for this repair on PBA. The genetics of PBA repair was investigated by observing the influence of the post-irradiation incubation medium (PBA vs BHI) on the number of streptomycin resistant mutants which develop in E. coli strains deficient in various repair pathways. A recB and recC strain (WP3 recB trp-; WP7 recC trp-) showed repair of potential streptomycin resistant mutants similar to that of B/r when incubated on PBA following irradiation. The medium had no effect on the number of mutants expressed in an excision deficient uvrA- strain (WP2 uvrA trp-) or a polymerase I mutant (P3478 polA thy-). This was interpreted to mean that the loss of streptomycin resistant mutants on PBA involves the excision repair pathway and is dependent on the polA gene product, polymerase I.

Culture Media↗
PubMed1989

Anterior and posterior, but not cheek, intraoral cannulation procedures elevate serum corticosterone levels in neonatal rat pups.

Implantation of intraoral cannulas is a procedure that has been typically assumed to be relatively unstressful in neonatal rat pups. To test this assumption, endocrine responses to such implantations were compared with those of other standard procedures. In Experiment 1, corticosterone and growth hormone (GH) levels were assessed in 4-day-old rat pups placed in an incubator for 15 or 60 min following either: no treatment, subcutaneous (sc) injection of 0.9% NaCl, anterior or posterior intraoral cannulation, ice anesthesia or ether anesthesia. Corticosterone levels were elevated relative to nontreated controls 15 min after all treatments except sc injection. These levels remained elevated after 60 min in both cannulation groups and the ice anesthesia group. In Experiment 2, the ability of ether anesthesia to reduce the hormonal response to the cannulation procedures was assessed in addition to examining the hormonal response to intraoral cannulations through the cheek in 4-day-old rat pups. Ether did not attenuate the corticosterone response to either anterior or posterior cannulations. Pups subjected to the cheek cannulation procedure did not exhibit any significant alterations in serum corticosterone levels when compared with nontreated control pups. GH levels were found to differentiate less among the various procedures than corticosterone levels, with GH levels generally being low in all groups, including nontreated control animals. These data suggest that a cheek placement is less stressful than anterior and posterior placements and may provide a viable alternative in studies necessitating the implantation of cannula into the buccal cavity during the early postnatal period.

Anesthesia, General↗
PubMed1989

Histamine-elicited drinking in weanling and adult rats.

A total of 260 male and female adult (60-70 days of age) and weanling (22-25 days of age) Sprague-Dawley derived rats were used in these experiments. Subcutaneous administration of histamine (HA) elicited drinking in a dose-dependent manner for both ages tested, although the threshold dose varied with age. A dose of 5.0 mg/kg HA elicited significant increases in water intake for adults, whereas for weanlings a dose of 20 mg/kg HA was necessary. Adult rats exhibited decreased latency to drink after all doses of HA tested, whereas for weanlings, decreased latency was evident only after doses of HA sufficient to elicit increases in water intake. Combined antagonism of H1 and H2 receptors for HA, using dexbrompheniramine and cimetidine, respectively, inhibited HA-elicited drinking in adults and weanlings. Further investigation of the ontogeny of histamine- and food-related drinking may provide a useful approach to examine the physiological mechanisms underlying fluid consumption in adult animals and as they are gradually elaborated during ontogeny.

Animals↗
PubMed1985

Disordered drinking in developing spontaneously hypertensive rats.

Eating and drinking in spontaneously hypertensive (SHR) and Wistar-Kyoto (WKY) rats were measured at 5-17 wk of life. The SHR drank significantly more water in 24 h than WKY as early as wk 9, spilled more dry food than did WKY, and exhibited an inverse relation between 24-h water intake and dry food spilled. When eating a meal of dry food after 12 h food deprivation, SHR drank earlier and drank more in a 1-h test than WKY rats. Moreover, SHR exhibited (as early as wk 7) a striking pattern of interrupting eating to drink. This pattern was not present when SHR ate liquid food, and it was attenuated by infusion of water through a cheek fistula. Adult SHR (22 wk) salivated less than WKY in response to intraperitoneal 3.25 mg/kg pilocarpine nitrate. When developing SHR and WKY were maintained on liquid and solid food, SHR gained disproportionately more weight than WKY during development. When young SHR were permitted to drink no more water than WKY rats, the development of hypertension was retarded, and body weight gain was slowed. Because restricted access to food, which produced an equivalent slowing of body weight gain as did restricted access to water, also retarded development of hypertension, it appears that restricted access to water retards development of hypertension due to delayed growth. These results demonstrate that hyperdipsia, apparently caused by deficient salivary function, is not necessary for the development of hypertension in SHR.

Animals↗
PubMed1984

Histamine plays a major role for drinking elicited by spontaneous eating in rats.

The effects of combined antagonism of H1 (using 1 mg/kg dexbrompheniramine IP) and H2 (using 16 mg/kg cimetidine IP) receptors for histamine prior to (a) drinking after 2.5 mg/kg histamine SC, (b) drinking after 1-hr water deprivation, and (c) drinking during spontaneous eating were examined at 1 hr into the dark phase of a 12:12'-hr light/dark cycle for 14 Sprague-Dawley male rats. Such antagonism of histamine receptors abolished drinking elicited by exogenous histamine without affecting drinking after water deprivation. Histaminergic antagonism did not affect spontaneous eating, but it appeared to abolish drinking prior to a meal (for only those 3 rats which exhibited such drinking), delayed the latency to initiate drinking after initiating a meal, and inhibited drinking which occurred during and after eating but prior to postprandial resting (i.e., satiety for food). Because antagonism of peripheral histamine receptors inhibited food-related drinking by over 60%, these results provide indirect support for the hypothesis that the preabsorptive food-contingent vagally-mediated release of gastric mucosal histamine plays a major role in spontaneous food-related drinking in the rat.

Animals↗
PubMed1980

Feasibility of testing DNA repair inhibitors for mutagenicity by a simple method.

A simple screening methodology for the determination of mutagenicity of DNA repair inhibitors has been tested in this laboratory. Radiation-resistant E. coli B/r and WP2 hcr+ and hcr- are suitable strains for mutagenicity testing. In these strains irradiated with 40-60 ergs/mm2, chemicals which interfere with repair of ultraviolet-induced pre-mutational lesions can be shown to enhance significantly the frequency of mutations to streptomycin resistance. This phenomenon is termed "mutational synergism" [18,20]. We have attempted to apply the procedure for securing data for "mutational synergism" between ultraviolet (UV) radiation and a number of antimalarial drugs including quinine hydrochloride (50 microgram/ml), quinine hydrobromide (50 microgram/ml), primaquine diphosphate (50 microgram/ml), chloroquine (50 microgram/ml), quinine (50 microgram/ml) and quinacrine dihydrochloride (25 microgram/ml). All drugs tested give synergistic effects with UV light. The synergistic activity ranges from 3- to 35-fold. Quinine and quinacrine dihydrochloride have been found to be much more efficient enhancers of the mutagenic effect of UV than caffeine. In general, we have found that the expression of synergistic action occurs at a concentration well below the minimum inhibitory concentration (MIC) with the drugs tested. The implication of these observations in the establishment of a screening method for the evaluation of the mutagenicity of DNA repair inhibitors is discussed.

DNA↗