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Biomedical subjects

D Rohrer

Publications and source records attributed to D Rohrer.

15 recordsLinked to original sources

Use of decompressive craniectomy after severe head trauma.

Ten percent of head injuries quality as "severe," requiring prompt diagnosis and treatment. This level I trauma center uses an aggressive approach to treatment of severe head injuries and, when indicated, intervenes with decompressive craniectomy. This article explains decompressive craniectomy, including indications, procedures, and protocols. The case studies presented highlight two patients with profound head injuries. Additionally, cranioplasty replacement of autograft flap is explained and discussed.

Adolescent↗

ERK plays a regulatory role in induction of LTP by theta frequency stimulation and its modulation by beta-adrenergic receptors.

MAP kinase (ERK) translates cell surface signals into alterations in transcription. We have found that ERK also regulates hippocampal neuronal excitability during 5 Hz stimulation and thereby regulates forms of long-term potentiation (LTP) that do not require macromolecular synthesis. Moreover, ERK-mediated changes in excitability are selectively required for some forms of LTP but not others. ERK is required for the early phase of LTP elicited by brief 5 Hz stimulation, as well as for LTP elicited by more prolonged 5 Hz stimulation when paired with beta1-adrenergic receptor activation. By contrast, ERK plays no role in LTP elicited by a single 1 s 100 Hz train. Consistent with these results, we find that ERK is activated by beta-adrenergic receptors in CA1 pyramidal cell somas and dendrites.

Action Potentials↗

The disparate effects of Alzheimer's disease and Huntington's disease on semantic memory.

Alzheimer's disease (AD) and Huntington's disease (HD) impair performance on semantic memory tasks, but researchers disagree on whether AD and HD cause these impairments in the same manner. According to one view, AD disrupts the storage of semantic memories, whereas HD disrupts the retrieval of semantic memories. Dissenters argue that AD, like HD, disrupts retrieval. In this study, participants generated category exemplars (e.g., kinds of fruits) for 1 min, and response latencies were examined. Relative to healthy controls, the 12 AD patients produced a larger proportion of responses earlier in the recall period, consistent with the view that AD patients quickly exhaust their limited supply of items in storage. By contrast, the 12 HD patients produced a larger proportion of their responses late in the recall period, consistent with the view that HD slows retrieval.

Aged↗

Promoter-activated expression of nerve growth factor for treatment of neurodegenerative diseases.

Genetic transfer approaches have received recent consideration as potential treatment modalities for human central and peripheral nervous system (CNS and PNS, respectively) neurodegenerative disorders, including Parkinson's disease, Alzheimer's disease, and amyotrophic lateral sclerosis. Transplantation of genetically modified cells into the brain represents a promising strategy for the delivery and expression of specific neurotrophic factors, neurotransmitter-synthesizing enzymes, and cellular regulatory proteins for intervention in neurodegenerative diseases. The use of specific regulatable promoters may also provide potential control of gene expression required for dose-specific or time-specific therapeutic strategies. In this article, we review the potential use of activated promoters in ex vivo systems for the potential genetic therapy of neurodegenerative disorders, and then describe our own studies using the zinc-inducible metallothionein promoter for the regulated expression of nerve growth factor (NGF) in rodent brain transplants.

Animals↗

Efficacy of a green tea extract rich in catechin polyphenols and caffeine in increasing 24-h energy expenditure and fat oxidation in humans.

BACKGROUND: Current interest in the role of functional foods in weight control has focused on plant ingredients capable of interfering with the sympathoadrenal system. OBJECTIVE: We investigated whether a green tea extract, by virtue of its high content of caffeine and catechin polyphenols, could increase 24-h energy expenditure (EE) and fat oxidation in humans. DESIGN: Twenty-four-hour EE, the respiratory quotient (RQ), and the urinary excretion of nitrogen and catecholamines were measured in a respiratory chamber in 10 healthy men. On 3 separate occasions, subjects were randomly assigned among 3 treatments: green tea extract (50 mg caffeine and 90 mg epigallocatechin gallate), caffeine (50 mg), and placebo, which they ingested at breakfast, lunch, and dinner. RESULTS: Relative to placebo, treatment with the green tea extract resulted in a significant increase in 24-h EE (4%; P < 0.01) and a significant decrease in 24-h RQ (from 0.88 to 0.85; P < 0.001) without any change in urinary nitrogen. Twenty-four-hour urinary norepinephrine excretion was higher during treatment with the green tea extract than with the placebo (40%, P < 0.05). Treatment with caffeine in amounts equivalent to those found in the green tea extract had no effect on EE and RQ nor on urinary nitrogen or catecholamines. CONCLUSIONS: Green tea has thermogenic properties and promotes fat oxidation beyond that explained by its caffeine content per se. The green tea extract may play a role in the control of body composition via sympathetic activation of thermogenesis, fat oxidation, or both.

Adipose Tissue↗

When two memories can and cannot be retrieved concurrently.

We examined whether two memories can be retrieved concurrently from long-term memory. In Experiment 1, the subjects recalled words, either from two categories--alternating between the two--or from just one category. In Experiment 2, the subjects recalled two words belonging to either the same category or different categories, and the category prompts for these two responses appeared either simultaneously or successively. The results of both studies are consistent with the view that two items from different categories must be retrieved serially, whereas two items from the same category can be retrieved in parallel.

Adult↗

On the relative and absolute strength of a memory trace.

Subjects studied either an 8- or 16-word list and later recalled the items while a voice key recorded each response latency. The trials were partitioned by recall total in order to examine the means and distributions of both latencies and interresponse times as a function of recall total. Each analysis was consistent with the view that an item's absolute strength determines whether it is recalled whereas an item's relative strength determines when it is recalled. In addition, mean latency was effectively proportional to study list length yet independent of recall total. All of the analyses were consistent with the view that the set of study items is sampled according to a relative-strength rule until all items are found and that a sampled item is recovered into consciousness only when its absolute strength exceeds a fixed threshold.

Adult↗

Retrieval from semantic memory and its implications for Alzheimer's disease.

In 3 experiments, participants generated category exemplars (e.g., kinds of fruits) while a voice key and computer recorded each response latency relative to the onset of responding. In Experiment 1, mean response latency was faster when participants generated exemplars from smaller categories, suggesting that smaller mental search sets result in faster mean latencies. In Experiment 2, a concurrent secondary task increased mean response latency, suggesting that slowed mental processing results in slower mean latencies. In Experiment 3, the mean response latency of Alzheimer's participants was faster than that of elderly controls, which is consistent with the idea that the semantic memory impairments of Alzheimer's disease patients stem primarily from a reduction in available items (as in Experiment 1) rather than retrieval slowing (as in Experiment 2).

Aged↗

An analysis of latency and interresponse time in free recall.

In four experiments, subjects freely recalled previously studied items while a voice key and computer recorded each item's recall latency relative to the onset of the recall period. The measures of recall probability and mean recall latency were shown to be empirically independent, demonstrating that there exists no a priori relationship between the two. In all four experiments, latency distributions were fit well by the ex-Gaussian, suggesting that retrieval includes a brief normally distributed initiation stage followed by a longer exponentially distributed search stage. Further, the variation in mean latency stemmed from the variation in the duration of the search stage, not the initiation stage. Interresponse times (IRTs), the time elapsed between two successive item recalls, were analyzed as well. The growth of mean IRTs, plotted as a function of output position, was shown to be a simple function of the number of items not yet recalled. Finally, the mathematical nature of both free recall latency and IRT growth are shown to be consistent with a simple theoretical account of retrieval that depicts mean recall latency as a measure of the breadth of search.

Adult↗

Congruency effects in part-list cuing inhibition.

In demonstrations of part-list cuing inhibition, subjects who are shown a subset of studied list words recall fewer noncue words than subjects not shown such part-list cues. We propose that part-list inhibition is governed in part by an incongruency principle: Inhibition occurs to the extent that part-list cues induce a retrieval framework different from that used to encode list items. In Experiment 1, word lists were studied followed by a test of free recall either without cues, or with cue words serially organized to be either congruent or incongruent with the order of studied items. In Experiments 2-4, cues consisted of every second study item in the original presentation order (congruent ones) or reordered to form famous names or familiar idioms that had been hidden in the study list (incongruent cues). More part-list inhibition was observed with incongruent cues than congruent cues in all 4 experiments.

Analysis of Variance↗

Age-induced decreases in the messenger RNA coding for the sarcoplasmic reticulum Ca2(+)-ATPase of the rat heart.

Age-associated slowing of cardiac relaxation related to the decline in the Ca2+ pump function of cardiac sarcoplasmic reticulum (SR) has been previously described. It is unclear if the decreased Ca2+ pump function results from a lower amount of Ca2(+)-ATPase protein or a decreased pumping activity of the enzyme. To determine if these alterations could be mediated by changes in the amount of the protein itself, the level of the messenger RNA (mRNA) coding for the Ca2(+)-ATPase of the SR of Fischer rat hearts (4- and 30-month-old rats) were quantitated with a Northern blotting technique. We observed that the levels of SR Ca2(+)-ATPase mRNA were 60% lower in old rats as compared with young rats, suggesting that a quantitative reduction in the levels of the corresponding protein could occur during aging to explain the delayed diastolic relaxation documented in old animals as opposed to a change in the specific activity of this enzyme. The thyroid hormone responsiveness of SR Ca2(+)-ATPase mRNA has been previously established. We have found in this study that the thyroxine levels were consistently lower in old rats; however, this difference was relatively small (4.3 +/- 0.7 and 3.1 +/- 0.8 micrograms/dl [mean +/- SD), respectively, in young and old rats). In addition, no age-induced decrease in 3,5,3'-triiodothyronine levels was observed, suggesting that the aging process itself may be responsible for the changes in SR Ca2(+)-ATPase mRNA levels.

Aging↗

Thyroid hormone markedly increases the mRNA coding for sarcoplasmic reticulum Ca2+-ATPase in the rat heart.

Previous findings have shown that thyroid hormone markedly increases the speed of diastolic relaxation in the heart. This thyroid hormone-dependent change is also accompanied by an increased Ca2+ pumping ability in the sarcoplasmic reticulum. In an effort to determine the underlying cause of improved Ca2+ transport, mRNA levels of the slow Ca2+-ATPase of the sarcoplasmic reticulum were quantified on Northern blots. In hypothyroid rat hearts, the steady state level of Ca2+-ATPase mRNA was only 36% of control levels, whereas hyperthyroid rat heart mRNA levels were 136% of control. Ca2+-ATPase mRNA responded rapidly to T3, as the mRNA level was significantly increased by 2 h and normalized by 5 h after T3 injection into hypothyroid rats. The well established effect of thyroid hormone on improved myocardial contractility and increased speed of diastolic relaxation may in part relate to specific alterations in the level of the mRNA coding for Ca2+-ATPase, resulting in increased pump units.

Animals↗

Thyroid hormone induced changes in cardiac proteins and mRNAs.

Contraction of the hypothyroid heart is characterized by delayed diastolic relaxation and decreased velocity of systolic contraction. In order to determine if these alterations could be mediated by the changes in the mRNA coding for the Ca++ ATPase of the sarcoplasmic reticulum and alterations of the mRNAs coding for myosin heavy chain (MHC) alpha and beta, the levels of these specific mRNAs were quantitated using a Northern blotting technique. We find that the Ca++ ATPase mRNA was 3-fold lower in hypothyroid hearts. After T3 administration to hypothyroid rats, Ca++ ATPase mRNA increased to 66% of control levels within 2 hrs and to 100% of control levels 5 hrs after T3 administration. In the hypothyroid heart, MHC beta mRNA was the predominant message with MHC alpha mRNA barely detectable. Administration of 2 mg of T3 led to a significant increase in MHC alpha mRNA levels first detectable 2 hrs after T3 administration. Twenty-four hrs after T3 administration, MHC alpha mRNA levels had normalized. The results of these studies indicate that thyroid hormone mediates significant alterations in the level of the mRNA coding for the Ca++ ATPase of the sarcoplasmic reticulum and of the mRNAs coding for MHC alpha and beta. Changes in the level of these specific mRNAs resulting in lower levels of the corresponding proteins may explain the delayed diastolic relaxation and the decreased velocity of contraction of the hypothyroid heart.

Animals↗

Progesterone derivatives that bind to the digitalis receptor: effects on Na+,K+-ATPase and isolated tissues.

The steroid nature of the cardiac glycosides (CG) suggests that an endogenous steroid (or steroids) may be the natural ligand for the specific receptor site, i.e., Na+,K+-ATPase. Derivatives of progesterone (PROG) that compete in a [3H]ouabain radioreceptor binding assay (RRA) are characterized by 17 alpha-acetylation and modifications in the B ring. Chlormadinone acetate (CMA) is the most potent analog identified thus far, having about one-twentieth the RRA potency of ouabain. CMA interacts at the ouabain site on Na+,K+-ATPase, inhibits the enzyme in the same rank order of species sensitivity as do the CG, and inhibits the sodium pump in vitro in guinea pig atrium and perfused heart, cardiac myocytes, rat diaphragm, and red blood cells. CMA does not cross-react with digoxin antiserum, which indicates that CG antibodies are not necessarily directed at molecular determinants of biological activity. By crystallographic analysis, the 20-carbonyl moiety in CMA is seen spatially oriented so as to be equivalent to the lactone 23-oxygen atom in the CG. CMA exerts primarily cardiodepressant effects, in accordance with the often-reported similar action of PROG. Negative inotropy may be mediated other than by Na+,K+-ATPase because PROG itself has no significant CG-like actions. Positive inotropy by CG, cardiodepression by CMA and PROG or low concentrations of CG, occasional transient enhancement of contractility by CMA, and pump stimulation by low concentrations of CMA or CG may reflect different affinities of the compounds for sites that mediate Na+,K+-ATPase/pump inhibition, positive inotropy, and negative inotropy. Thus, PROG derivatives related to CMA appear to be likely candidates for endogenous digitalis-like hormones. Body tissues possess the enzymes for conversion of PROG to derivatives related even more closely than the semisynthetic CMA to the CG configuration.

Animals↗