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Biomedical subjects

A Keller

Publications and source records attributed to A Keller.

At least 199 records · Page 11Linked to original sources
PubMed1989

Long-term potentiation in the motor cortex.

Long-term potentiation (LTP) is a model for learning and memory processes. Tetanic stimulation of the sensory cortex produces LTP in motor cortical neurons, whereas tetanization of the ventrolateral nucleus of the thalamus, which also projects to the motor cortex, does not. However, after simultaneous high-frequency stimulation of both the sensory cortex and the ventrolateral nucleus of the thalamus, LTP of thalamic input to motor cortical neurons is induced. This associative LTP occurs only in neurons in the superficial layers of the motor cortex that receive monosynaptic input from both the sensory cortex and the ventrolateral nucleus of the thalamus. Associative LTP in the motor cortex may constitute a basis for the retention of motor skills.

Animals↗
PubMed1989

Triads: a synaptic network component in the cerebral cortex.

The objective of this study was to examine synaptic relationships among 3 neuronal elements in the cerebral cortex: thalamocortical afferents (TC), corticothalamic projection cells (CT), and GABAergic neurons. TC axon terminals in the barrel cortex of the mouse were labeled by lesion induced degeneration; local axon collaterals belonging to CT cells were labeled by the retrograde transport of horseradish peroxidase; and GABAergic neurons were identified using immunocytochemistry. CT and GABAergic neurons form synapses with each other and both receive synapses from TC afferents. These findings indicate the existence in the cerebral cortex of a triadic circuit involving afferent input both to projection and to local inhibitory neurons, and reciprocal synaptic interactions among these neuronal populations.

Animals↗
PubMed1989

Thalamocortical synapses with identified neurons in monkey primary auditory cortex: a combined Golgi/EM and GABA/peptide immunocytochemistry study.

The objective of this study was to identify neurons in layer IV of the monkey primary auditory cortex (area KA) that are postsynaptic to thalamocortical axon terminals. Thalamocortical axon terminals were labeled by lesion-induced degeneration; neurons postsynaptic to these afferents were labeled by the Golgi/EM method followed by postembedding immunocytochemistry. Five of the six non-pyramidal neurons examined received synapses from thalamocortical axon terminals. All of these cells were immunoreactive for gamma-aminobutyric acid (GABA). One of the cells stained also with an antiserum to somatostatin, and another for cholecystokinin. None of the cells examined were immunoreactive to substance P, and in no instance were two different peptides co-localized within the same GABA-positive neuron.

Animals↗
PubMed1989

A multicenter evaluation of the safety, tolerability, and efficacy of isradipine in the treatment of essential hypertension.

Six hundred outpatients aged between 22 and 84 years with essential hypertension (diastolic blood pressure of at least 95 mm Hg) entered a multinational, multicenter, single-blind trial with dose titration to assess the safety, tolerability, and efficacy of isradipine in doses of 1.25, 2.5, and 5.0 mg twice daily over 12 weeks, following a two-week placebo run-in period. Isradipine alone was taken by 321 patients, the remainder receiving, in addition, other antihypertensive drugs. In valid patients receiving monotherapy, the mean final isradipine dose was 3.4 mg (median, 2.5 mg) twice daily, which normalized supine diastolic blood pressure in 85 percent and 64 percent of patients two to four hours and 10 to 14 hours post-dose, respectively. Overall, 242 patients (40 percent) reported adverse events, 39 (7 percent) of whom withdrew from the study for this reason. The most common side effects were flushing (11 percent), headache (10 percent), and localized edema (4 percent). None of the pathologic changes in hematologic or biochemical values was attributable to isradipine. It is concluded that a slow titration of isradipine by increments at three-week intervals results in an effective and well-tolerated treatment for essential hypertension, both in mono- and combination therapy.

Adult↗
PubMed1989

Elevation of plasma epinephrine concentrations inhibits proteolysis and leucine oxidation in man via beta-adrenergic mechanisms.

The role of elevated plasma epinephrine concentrations in the regulation of plasma leucine kinetics and the contribution of beta-receptors were assessed in man. Epinephrine (50 ng/kg per min) was infused either alone or combined with propranolol (beta-blockade) into groups of six subjects fasted overnight; leucine flux, oxidation, and net plasma leucine forearm balance were determined during 180 min. Constant plasma insulin and glucagon concentrations were maintained in all studies by infusing somatostatin combined with insulin and glucagon replacements. Plasma leucine concentrations decreased from baseline during epinephrine infusion by 27 +/- 5 mumol/liter (P less than 0.02) due to a 22 +/- 6% decrease in leucine flux (P less than 0.05 vs. controls receiving saline) and to an increase in the metabolic clearance rate of leucine (P less than 0.02). Leucine oxidation decreased by 36 +/- 8% (P less than 0.01 vs. controls). beta-Blockade abolished the effect of epinephrine on leucine flux and oxidation. Net forearm release of leucine increased during epinephrine (P less than 0.01), suggesting increased muscle proteolysis; the fall of total body leucine flux was therefore due to diminished proteolysis in nonmuscle tissues, such as splanchnic organs. Nonoxidative leucine disappearance as a parameter of protein synthesis was not significantly influenced by epinephrine. Plasma glucose and FFA concentrations increased via beta-adrenergic mechanisms (P less than 0.001). The results suggest that elevation of plasma epinephrine concentrations similar to those observed in severe stress results in redistribution of body proteins and exerts a whole body protein-sparing effect; this may counteract catabolic effects of other hormones during severe stress.

Adrenergic beta-Antagonists↗
PubMed1989

[Videodensitometry analysis of stomach wall motility--presentation of a new method].

The videodensitometry is a suitable method for recording the gastric wall motility. It provides biosignals amenable by computer. There are no special demands to any organic form or kind of contraction. The asymmetry of the stomach makes no difference, therefore. The hitherto usual manometry will not be superseded. Both methods complete themselves in an ingenious manner. The radiation exposure by videodensitometry can be diminished by modifying the system for image causation.

Absorptiometry, Photon↗
PubMed1988

Types and distribution of glutamic acid decarboxylase (GAD)-immunoreactive neurons in mouse motor cortex.

Neuronal structures in mouse motor cortex that contain gamma-aminobutyric acid (GABA), were identified by an immunocytochemical method, using an antiserum to glutamic acid decarboxylase (GAD). GAD-positive cell bodies occurred in all layers of the motor cortex, but were more concentrated in layers III and VI. GAD-positive puncta, presumably axon terminals, were also distributed throughout the cortical layers; a high density of puncta occurred in layer III, whereas a somewhat lower density characterized layer VI. Based on the shapes of their somata and dendritic trees we concluded that all GAD-positive cells were of the non-pyramidal type.

Animals↗
PubMed1988

Evaluation of the cytotoxic activity of diethylstilbestrol and its mono- and diphosphate towards prostatic carcinoma cells.

To evaluate a possible direct cytotoxic effect of diethylstilbestrol diphosphate (DESDP) in the treatment of prostate cancer we exposed three prostatic carcinoma cell lines (LNCaP, DU 145, and PC-3), 2 nonprostatic neoplastic cell lines (KB and EJ), and one nontransformed cell line (MRC-5) to diethylstilbestrol (DES), diethylstilbestrol monophosphate, and DESDP at levels occurring in patients' sera during p.o. DES therapy (2 to 5 ng/ml) or DESDP infusions (1 to 20 micrograms/ml), respectively. With 5 ng/ml of DES no effect was seen in LNCaP cells, even after 14 days of exposure. In contrast, drug levels attained during DESDP infusions showed marked, dose-dependent cytotoxicity towards all cell lines under study. Prostatic cells were not exceptionally sensitive. High-dose DES slightly stimulated the synthesis of prostatic acid phosphatase in LNCaP cells. Formation of foci of polygonal cells was induced by 5 micrograms/ml of DES in cultures of MRC-5 fibroblasts. We conclude that, at high doses, DES liberated from DESDP acts upon a regulatory or metabolic mechanism common to many if not all human cells. Preferential sensitivity of prostate cancer cells in vivo may be due to high local phosphatase activity and/or DES accumulation in prostatic tissue.

Acid Phosphatase↗
PubMed1988

2-Aminopurine selectively inhibits the induction of beta-interferon, c-fos, and c-myc gene expression.

The protein kinase inhibitor 2-aminopurine (2AP) blocks the induction of the human beta-interferon gene by virus or poly(I)-poly(C) at the level of transcription. This inhibition is specific, since 2AP does not inhibit induction of either the hsp70 heat-shock gene by high temperature or the metallothionein gene by cadmium or dexamethasone. However, 2AP does block the induction of the c-fos and c-myc proto-oncogenes by serum growth factors or virus, suggesting that a protein kinase may be involved in the regulation of these genes, as well as of the beta-interferon gene. However, different factors must be required for the induction of these three genes, since they are not coordinately regulated by the same inducers in most of the cell lines examined.

2-Aminopurine↗
PubMed1988

Toxicity and response to high-dose ifosfamide + mesna as salvage therapy for advanced breast cancer.

Twenty-six cycles of high-dose ifosfamide + mesna (HD-IFO + M) were applied to seven female patients with advanced breast cancer refractory to prior treatment, using three different durations of continuous infusion (4, 24, and 48 h) every 3 weeks. To evaluate the most tolerable time schedule, the duration of the infusions was changed periodically in each patient. Toxicity was low in general, but continuous infusion of HD-IFO + M over 24 h appeared to be the best tolerated. One partial response lasting 27 weeks was achieved and four patients achieved stable disease lasting from 9 to 12 weeks.

Adult↗
PubMed1987

Synaptic organization of GABAergic neurons in the mouse SmI cortex.

Immunocytochemical methods were used to examine GABAergic neurons in the barrel region of the mouse primary somatosensory cortex. GABAergic neurons occur in all layers of the barrel cortex but are more concentrated in the upper portion of layers II/III and in layers IV and VI. Nine cells in layer IV were examined with the electron microscope, and portions of their dendrites were reconstructed from serial thin sections. These cells are of the nonspiny, multipolar or bitufted varieties, and some of them have beaded dendrites. The labeled cell bodies and their reconstructed dendrites were postsynaptic at asymmetrical synapses with thalamocortical axon terminals labeled by lesion-induced degeneration and with unlabeled axon terminals. Each cell also received symmetrical synapses from GABAergic axon terminals and from unlabeled axon terminals. Our results indicate that GABAergic cell bodies and processes receive synapses from thalamocortical axon terminals but that different cells display marked differences in the proportion of thalamocortical and other synapses they receive. These results indicate that GABAergic cells form a heterogeneous population with respect to their morphologies and patterns of synaptic inputs. The synaptic sequences revealed here for GABAergic neurons represent an anatomical substrate for various inhibitory processes known to occur within the cerebral cortex.

Animals↗
PubMed1987

Intrinsic circuitry involving the local axon collaterals of corticothalamic projection cells in mouse SmI cortex.

The objective of this study was to identify the components involved in a local synaptic circuit in the mouse cerebral cortex. The local axon collaterals of corticothalamic (CT) projection cells in the posteromedial barrel subfield area of primary somatosensory cortex were labeled by the retrograde transport of horseradish peroxidase injected into the ipsilateral thalamus. Thalamocortical (TC) axon terminals in the same region of cortex were labeled by lesion induced degeneration. CT axon terminals synapsed preferentially with dendritic shafts, whereas TC axon terminals synapsed mainly with dendritic spines. Some dendrites received both CT and TC synapses. Dendrites were interpreted to belong to nonspiny multipolar cells. These results indicate that a reciprocal synaptic relationship exists in the cortex between nonspiny multipolar cells and CT projection cells. Both CT projection cells and nonspiny multipolar neurons have been shown previously to receive TC synapses (White and Hersh: J. Neurocytol. 11:137-157, '82; White, Benshalom, and Hersch: J. Comp. Neurol. 229:311-320, '84). These findings imply that a triadic relationship involving afferent input and populations of CT projection and intrinsic neurons is a basic feature of the synaptic organization of the cerebral cortex.

Animals↗
PubMed1987

Assessment of function in routine clinical practice: description of the COOP Chart method and preliminary findings.

The COOP Project, a primary care research network, has begun development of a Chart method to screen function quickly. The COOP Charts, analogous to Snellen Charts, were pretested in two practices on adult patients (N = 117) to test feasibility, clinical utility, and validity. Patients completed questionnaires containing validated health status scales and sociodemographic variables. Practice staff filled out forms indicating COOP Chart scores and clinical data. We held debriefing interviews with staff who administered the Charts. The results indicate the Charts take 1-2 minutes to administer, are easy to use, and produce important clinical data. The patterns of correlations between the Charts and validity indicator variables provide evidence for both convergent and discriminant validity. We conclude that new measures are needed to assess function in a busy office practice and that the COOP Chart system represents one promising strategy.

Activities of Daily Living↗
PubMed1986

Molecular cloning of the avian beta-nerve growth factor gene: transcription in brain.

A chicken gene cross-hybridizing with a murine beta-nerve growth factor (beta NGF) cDNA probe was identified by Southern blot analysis and isolated from a genomic DNA library. The DNA sequence coding for the putative mature beta NGF protein was determined, providing direct evidence for the existence in birds of a neurotrophic factor sharing a high degree of sequence homology with mammalian beta NGF. In addition this gene is shown to be transcriptionally active in adult avian brain as demonstrated by Northern blot analysis.

Animals↗
PubMed1986

Distribution of glutamic acid decarboxylase-immunoreactive structures in the barrel region of mouse somatosensory cortex.

Neuronal structures in the barrel region of the mouse primary somatosensory cortex containing gamma-aminobutyric acid (GABA) were identified by an immunocytochemical method, using an antiserum to glutamic acid decarboxylase (GAD), the rate-limiting enzyme in the synthesis of GABA. GAD-positive cell bodies were found in all layers of the barrel cortex, but were more concentrated in the upper portion of layer II/III, and in layers IV and VI. Puncta, presumably axon terminals, were also distributed throughout the cortical layers; a high density of puncta occurs in layer IV, whereas a somewhat lower density characterizes layer VI. Based on the shapes of their somata and the distribution of their dendrites it was determined that all GAD-positive cell bodies were of the non-pyramidal type.

Animals↗