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Biomedical subjects

R T Dunn

Publications and source records attributed to R T Dunn.

At least 37 records · Page 2Linked to original sources
PubMed1998

A history of the use of anticonvulsants as mood stabilizers in the last two decades of the 20th century.

Anticonvulsants have moved into an important position as alternatives and adjuncts to lithium carbonate in the treatment of bipolar illness. Work with the nonhomologous model of kindled seizures helped in the choice of carbamazepine as a potential mood stabilizer and in the study of the mechanisms of action of the second generation anticonvulsants carbamazepine and valproate, as well as the putative third generation psychotropic anticonvulsants lamotrigine and gabapentin. Anticonvulsant neuropeptides such as TRH and nonconvulsant approaches with repeated transcranial magnetic stimulation (rTMS) also appear promising.

Anticonvulsants↗
PubMed1998

Tissue-specific expression of rat sulfotransferase messenger RNAs.

The present study examined the tissue distribution of rat sulfotransferase (SULT) mRNAs to assess the relative contribution of each tissue to the process of sulfation. The SULT isoforms examined were male-dominant SULTs (SULT1A1, SULT1C1, and SULT1E2), female-dominant SULTs (SULT20/21, SULT40/41, and SULT60), and the recently cloned, non sex-dependent SULT (SULT1B1). SULTs fall into two distinct classes based on substrate preference: phenol SULTs (SULT1A1, SULT1B1, SULT1C1, and SULT1E2) and hydroxysteroid SULTs (SULT20/21, SULT40/41, and SULT60). The following tissues were analyzed for SULT mRNA expression: liver, brain, lung, heart, intestine, kidney, adrenal, prostate, testes, ovary, uterus, and spleen by Northern blot analysis with [alpha-32P]dATP-labeled oligonucleotide probes specific for individual SULT mRNAs. Tissue expression levels of each SULT were quantified and compared with liver expression by phosphor-autoradiographic analysis. Male-dominant SULT expression was observed in many organs, where SULT1A1 was expressed in liver, brain, lung, heart, intestine, kidney, adrenal, testes, and spleen; SULT1C1 expression was observed in liver, kidney, and spleen; and SULT1E2 expression was observed only in liver and heart. The female-dominant SULTs exhibited a more limited tissue distribution. Expression of SULT20/21 and SULT60 was observed only in liver and adrenal gland, whereas SULT40/41 expression was observed only in liver. SULT1B1 was expressed to a similar extent in tissues of male and female rats and was detected in liver, intestine, and kidney. Expression of SULT mRNAs in liver was much higher than in other tissues, except for SULT1A1, which exhibited substantial expression in lung, and SULT1B1, which was expressed at relatively high levels in intestine. These studies indicate that liver is the most diverse organ with respect to expression of multiple SULT enzymes and is therefore the most significant organ involved in sulfation. In contrast to liver, extrahepatic tissues express specific SULT mRNAs, and this may be important for the physiological role of each tissue.

Animals↗
PubMed1997

[Are convulsions necessary for the antidepressive effect of electroconvulsive therapy: outcome of repeated transcranial magnetic stimulation].

Sismotherapy (ST) brings about numerous neurobiological changes, particularly changes in neuromediators and their receptors, second messengers, neuropeptides and neurotropic factors, a number of which are hypothesized to play a role in the pathophysiology or therapeutics of affective disorders (M. Fink). What is not yet known is which of these mechanisms is crucial for the psychotropic and anticonvulsant effects of ST. However, it is clear that the effects of ST tend to be relatively acute, and do not attack the deep-seated abnormalities that are the underlying causes of recurrences of affective disorders. This is corroborated by the fact that in animals, most of the effects of ECS on catecholamines and their receptors (and on receptors for benzodiazepines or neuropeptides such as TRH) tend to be relatively transient, and in most cases have been found to represent compensatory adaptations to the induced motor convulsions. However, recent preclinical data using attenuation, and clinical findings using reiterated transcranial magnetic stimulation (rTMS), suggest that it may not be necessary to provoke a clonic convulsion in order to achieve the beneficial psychotropic and anticonvulsant effects of ST. In rodents receiving stimulation to the cerebellar tonsil, seven daily subacute low-frequency sessions (stimulation at 1 Hz for 15 minutes) produced clear improvement in clonic convulsions and in post-discharge thresholds, together with durable inhibition of convulsions when stimulation was resumed (Weiss et al., 1995). Stimulation at 1 Hz for 15 minutes was more effective than stimulation at 10 or 20 Hz in attenuating convulsions. Although reiterated ECS also induced an anti-triggering effect, this dissipated rapidly over five days (Post et al., 1984). It is of great interest that recent publications have shown that rTMS at 10 or 20 Hz to the left frontal cortex, administered to patients suffering from refractory depression (George et al., 1995) or to patients (hospitalised or not) with milder degrees of depression (Pasquale-Leon et al., 1996), had a moderate or marked antidepressant effect. In these studies, rTMS showed few unwanted effects (other than mild pain in some patients, due to contraction of the temporal muscles); it did not induce motor convulsions, and did not, as such, appear to be associated with the memory loss described in subjective accounts or in preliminary neuropsychological tests (Little and Kimbrell et al., 1996). The optimal frequencies, durations and positions for rTMS to maximise its antidepressant effect still remain to be determined. However, the first controlled and open studies have tended to show that (because of the capacity of rapid magnetic fluxes to produce sub-convulsant electrical discharges that are relatively localised in the brain), rTMS may be found to be a clinically useful antidepressant model. This would suggest the possibility that some of the neurochemical changes induced by the clonic convulsions of ECS could be directly induced by stimulation at the very edge of the threshold (but still below it); this would open up the hope that one day these endogenous neurochemical processes could be identified and exploited in an optimal way for therapeutic purposes.

Brain↗
PubMed1996

Purification and characterization of an Ah receptor binding factor in chromatin.

Dioxin induces biological responses through interaction with a specific intracellular receptor, the Ah receptor, and the subsequent interaction of the Ah receptor with chromatin. We previously reported the binding of the Ah receptor, partially purified form rabbit liver, to receptor binding factors (termed AhRBFs) in chromatin. Rabbit liver chromatin proteins (CP) were isolated by absorption of chromatin to hydroxylapatite followed by sequential extraction with 3 M NaCl and 1-8 M guanidine hydrochloride (GdnHCl). In the present study, we continued the purification of the CP5 fraction, which exhibited AhRBF activity. The proteins in CP5 were separated by CL-Sepharose 6B column chromatography resolving lower molecular weight fractions. To assay for receptor binding, a portion of each Cl-Sepharose 6B fraction was reconstituted to rabbit double-stranded DNA (dsDNA) using a reverse gradient dialysis of 7.5 to 0.0 M GdnHCl. These reconstituted chromatins were then examined for binding to [3H]-2,3,7,8-tetrachlorodibenzo-p-dioxin ([3H]TCDD)-receptor complexes by the streptomycin filter binding assay. Two protein fractions with a molecular weight in the range of 10,000-14,000 demonstrated high affinity binding to the Ah receptor. The binding of AhRBFs reconstituted to dsDNA was shown, by competition experiments with Ah receptor bound by unlabeled TCDD (TCDD-R), to be > 90% specific for [3H]TCDD-R. Further purification was achieved by preparative ADS-PAGE, and AhRBF activity was attributed to two fractions with molecular weights between 12,000 and 10,000. A kDa protein with AhRBF activity was found to have an isoelectric point (pI) of > or = 10. The 12 kDa AhRBF was sequenced by Edman degradation after cyanogen bromide cleavage and identified as histone H4. Although histone H4 has been postulated to interact with transcription factors in a variety of systems, this is the first report of a specific interaction of AhR with histone H4.

Amino Acid Sequence↗
PubMed1993

Binding of the Ah receptor to receptor binding factors in chromatin.

Dioxin induces biological responses through interaction with a specific intracellular receptor, the Ah receptor, and the subsequent interaction of the Ah receptor with chromatin. We report the binding of the Ah receptor, partially purified from rabbit liver, to receptor binding factors in chromatin. Rabbit liver chromatin proteins (CP) were isolated by adsorption of chromatin to hydroxylapatite followed by sequential extraction with 1-8 M GdnHCl. To assay for receptor binding a portion of each CP fraction was reconstituted to rabbit double-stranded DNA using a reverse gradient dialysis of 7.5 to 0 M GdnHCl. These reconstituted nucleoacidic proteins were then examined for binding to [3H]-2,3,7,8-tetrachlorodibenzo-p-dioxin ([3H]TCDD)-receptor complexes by the streptomycin filter assay. Prior to the binding assay, [3H]TCDD-receptor complexes were partially purified by step elution from DEAE-cellulose columns. CP fractions 2, 5, and 7 were found to bind to the Ah receptor with high affinity. Scatchard analysis yielded Kd values in the nanomolar range. Competition with 2-fold excess unlabeled TCDD-receptor complexes was demonstrated, and binding was reduced markedly when the receptor was prepared in the presence of 10 mM molybdate. Such chromatin receptor binding factors (RBFs) may participate in the interaction of receptor with specific DNA sequences resulting in modulation of specific gene expression.

Animals↗
PubMed1993

Effects of salbutamol upon performance on an operant screen for antidepressants.

The beta adrenergic (beta) agonist salbutamol increased reinforcement rates and decreased response rates on a differential-reinforcement-of-low-rate (DRL) 72-S schedule. These changes in DRL 72-S schedule performance are also produced by most clinically used antidepressants. The effects of salbutamol on a DRL 72-S schedule were dose-dependently antagonized by the beta antagonist metoprolol, but not changed by the 5HT antagonist methysergide. Additionally, neither salbutamol nor the antagonism of salbutamol by metoprolol caused disruption of DRL 72-S schedule performance. These results indicate that stimulation of beta receptors, and not of 5HT receptors, mediates salbutamol antidepressant-like effects on a DRL 72-S schedule.

Albuterol↗
PubMed1993

F:\DOCS\DOCS--physicians and automation.

While a paperless system may not be commonplace today, strides are being taken by groups such as CPRI to ensure the development of such a system. Several hospitals and clinics are moving toward or have implemented paperless or limited paper environments using patient-centered systems where charting is performed at the "bedside" of the patient through sophisticated software and hardware systems. Such systems will continue to evolve until the ATM of patient care is created. At that time, patients' access to their own information will be an acceptable phenomenon, physician use of computers will be commonplace, acceptance that adjunct knowledge bases must be coupled with the human skills of the physician, and test redundancy will be considered intolerable. These steps will contribute to the cost reductions needed to truly "reform" health care and create a value-added product for the United States.

Attitude to Computers↗
PubMed1992

Transcription--the untamed frontier.

Health information managers must be more aggressive in defining the technology and standards for dictation and transcription equipment and services. The author offers many ideas on how to tame the technology jungle out there!

Contract Services↗
PubMed1985

Effects of 72 hr calf removal and/or gonadotropin releasing hormone on luteinizing hormone release and ovarian activity in postpartum beef cows.

A study was conducted to determine the pituitary and ovarian responses to 72 hr calf removal (CR) and/or gonadotropin releasing hormone (GnRH) in beef cows. Forty-eight Angus, Simmental, and Charolais crossbred cows in moderate body condition were allotted to an experiment of 2x2 factorial design involving CR and GnRH. At 30 to 32 days postpartum, calves were removed for 72 hr from the CR and CR plus GnRH groups. All cows were injected (i.m.) with saline or 200 microg of GnRH at 33 to 35 days postpartum. Saline or GnRH was injected 5 hr before calf return. Plasma luteinizing hormone (LH) was measured in blood samples collected every 30 min for 5.5 hr beginning 30 min prior to injection of saline or GnRH. Plasma progesterone was measured in blood samples collected 0, 7, and 14 days after GnRH injection and 7 and 14 days following the first detected estrus. There were no differences (P>0.05) in the interval to peak LH release or the magnitude of the LH release between the GnRH and CR plus GnRH groups; however, the GnRH induced release of LH was greater (P<0.05) over time when preceded by CR. Plasma progesterone concentrations were increased on day 7, compared to day 0, after GnRH injection in 57% and 50% of the animals in the GnRH and CR plus GnRH groups, respectively. However, behavioral estrus was not observed in any of the cows between days 0 and 7 after GnRH injection. A higher (P<0.05) percentage of the cows injected with GnRH formed luteal tissue compared to cows injected with saline; however, the luteal lifespan following GnRH injection was decreased relative to the luteal lifespan following the first observed estrus. The mean interval from calving to first estrus was decreased (P<0.05) by 17 days in the CR group relative to the other groups, and calf removal had no detrimental effect on milk production at 80 days postpartum or on calf weaning weights at approximately 7 months of age. In summary, 72 hr CR decreased the postpartum interval and increased the pituitary responsiveness to GnRH. Pretreatment with 72 hr CR did not alter circulating progesterone concentrations or luteal lifespan of corpora lutea induced by GnRH.

Journal Article↗