Insights into associative long-term potentiation from computational models of NMDA receptor-mediated calcium influx and intracellular calcium concentration changes.

1. Because induction of associative long-term potentiation (LTP) in the dentate gyrus is thought to depend on Ca2+ influx through channels controlled by N-methyl-D-aspartate (NMDA) receptors, quantitative modeling was performed of synaptically mediated Ca2+ influx as a function of synaptic coactivation. The goal was to determine whether Ca2+ influx through NMDA-receptor channels was, by itself, sufficient to explain associative LTP, including control experiments and the temporal requirements of LTP.

Selection for transformation and met protooncogene amplification in NIH 3T3 fibroblasts using tumor necrosis factor alpha.

Alterations in the structure and expression of protein tyrosine kinases are associated with cellular transformation and tumorigenicity. These enzymes may contribute to tumor progression by interfering with host mechanisms of antitumor surveillance. In the present work, we show that selection of NIH 3T3 fibroblasts for resistance to the cytotoxic effects of tumor necrosis factor alpha (TNF-alpha), a major mediator of macrophage-induced tumor cell cytotoxicity, leads to enrichment in the remaining cells for those with transformed morphology and is often associated with amplified copy number and expression of the met protooncogene.

Screening elder cardiac patients to identify need for social work services.

Present screening methods to identify older patients in need of posthospital care planning are overly sensitive and lack specificity, with the rate of false-positive screenings reaching 65 percent. Research was undertaken to develop a computerized screening mechanism to identify elderly cardiac patients at high risk for posthospital care needs. Using the data from the Medicus Nursing Productivity and Quality of Patient Care Classification System (NPAQ) as potential predictive factors, the false-positive screening rate was reduced to 26 percent.

Temperature dependence of circadian rhythms in golden-mantled ground squirrels.

We tested the hypothesis that the free-running period and phase angles of entrainment of circadian locomotor activity rhythms of golden-mantled ground squirrels (Spermophilus lateralis) vary as a function of body temperature (Tb). Animals were maintained in a light-dark cycle (LD 14:10), and at 6-week intervals ambient temperature (Ta) was changed from 20 degrees to 30 degrees C, or vice versa. Data were collected during the animals' homeothermic and heterothermic phases.

A comparative double-blind randomised study of single dose fosfomycin trometamol with trimethoprim in the treatment of urinary tract infections in general practice.

A double-blind, double-dummy trial comparing a single dose treatment with fosfomycin trometamol (FT, 3 g) versus trimethoprim (TMP, 200 mg) was carried out in women with uncomplicated urinary tract infections. From 51 clinically evaluable patients, 44 were bacteriologically assessable at the 6-week follow-up. The results were as follows in the FT group (n = 22): eradication in 17 (77.

Effects of uniform and non-uniform synaptic 'activation-distributions' on the cable properties of modeled cortical pyramidal neurons.

Knowledge of the resting potential and input resistance reveal little about the electrotonic structure of nerve cells since that structure is governed by the background distribution of activated conductances. The background distribution of activated conductances (or 'activation-distribution') is commonly assumed to be uniform, but there is much evidence to suggest that the 'activation-distribution' of cortical pyramidal cells in non-uniform. We investigated effects of uniform and non-uniform activation-distributions with simulations employing passive cable models of an HRP-injected cortical pyramidal neuron.

Pre-natal development of the adrenal gland in the mallard duck (Anas platyrhynchos).

The differentiating nephrotome in the 10-day-old mallard duck embryo is able to synthesize corticosterone, aldosterone and deoxycorticosterone even though an adrenal anlage cannot be identified histologically until the 12th day of incubation. At this time, sudanophilic cells containing much smooth endoplasmic reticulum and numerous mitochondria with tubular cristae are located adjacent to the developing mesonephros. Chromaffin cells appear in this region on about the 14th day of embryogenesis.

Neuroleptic and anti-depressant drug treatment abolishes conditioned immunosuppression in mice.

Mice previously exposed to cyclophosphamide in the presence of saccharin-flavored water will show a decreased antibody response to challenge with sheep erythrocytes if simultaneously they are again given saccharin to drink. These mice also show conditioned taste aversion. Treatment of conditioned animals with chlorpromazine or amitriptyline after challenge with erythrocytes in the presence of saccharin reduced the degree of immunosuppression and, though to a lesser degree, the conditioned taste aversion.

The relationship of early risk and current mediators to depressive symptomatology in adolescence.

In an ongoing 10-year longitudinal study in a lower-middle-class community, 21% of 378 fifteen-year-olds studied through interviews and questionnaires reported high levels of depressive symptoms on the Children's Depression Inventory. Girls were twice as likely to express depressive symptoms as boys. Early risk factors for high levels of depressive symptomatology included serious preschool illness, anxiety expressed at age 9, and death of a parent for girls but not boys.

Nucleotide sequence of the Escherichia coli tRNA(3Leu) gene.

A 300-nucleotide sequence was determined which includes the tRNA(3Leu) coding region and the flanking sequences.

Flanking sequences are required for efficient transcription and stable complex formation for the human tRNAiMet3-coding gene.

An analysis of 5' and 3' deletions of the human tRNAiMet3 gene has revealed upstream regions required for efficient transcription and stable complex formation in vitro. The 5' boundary of this essential region lies between nucleotides -39 to -18 (start point = + 1), and it has been shown that 3'-flanking sequences near the first termination site are also important for stable complex formation. The transcriptional efficiency of two non-allelic loci (TMET3 and TMET2) has been compared and TMET2 is more active.

An aminopyridine-sensitive, early outward current recorded in vivo in neurons of the precruciate cortex of cats using single-electrode voltage-clamp techniques.

Studies were performed in cortical neurons to determine if voltage- and time-dependent membrane currents could be recognized and characterized in the dynamic, in vivo state. Intracellular measurements made in neurons of the precruciate cortex of awake cats with single-electrode voltage-clamp (SEVC) techniques disclosed an early outward current to depolarizing command steps in 124 of 137 cells studied. The voltage-dependent properties of the early outward current closely resembled those of A-currents studied in vitro in vertebrate and invertebrate neurons.

The role of dendritic diameters in maximizing the effectiveness of synaptic inputs.

The role of dendritic diameters in maximizing the effectiveness of synaptic inputs was examined in a cell represented as a single cylinder and in a cortical pyramidal cell using mathematical models and computer stimulations. For current input into one end of a cylinder of fixed physical length, the maximum potential at the other end of the cylinder was obtained when the cylinder diameter was chosen so that the electrotonic length, L, of the cylinder was 2.98.

Metabolism of aldosterone in the colostomized duck (Anas platyrhynchos): partial characterization of urinary metabolites.

1. Chronically colostomized ducks were injected with [4-14C]-aldosterone to study the metabolism of aldosterone and the pattern of metabolite excretion via the kidney. 2.

Changes in the adrenal steroidogenic responsiveness of the mallard duck (Anas platyrhynchos) during early post-natal development.

1. Plasma concentrations of corticosterone (B), aldosterone (Aldo) and deoxycorticosterone (DOC) were measured in mallard ducklings immediately before and after exposure to acute immobilization stress. 2.

Mating of captive thirteen-lined ground squirrels and the annual timing of estrus.

Thirteen-lined ground squirrels (Spermophilus tridecemlineatus) have a single annual mating season in Michigan, beginning shortly after their spring emergence from hibernation. Captive females were studied during a 3-year period to determine relations among time of removal from the coldroom, vaginal estrus, and mating behavior. Following a 7-month period females spent in a coldroom, vaginal lavages were taken daily to monitor changes in estrous condition.

Midazolam sedation for outpatient fibreoptic endoscopy: evaluation of alfentanil supplementation.

Alfentanil, a short-acting opioid, was used as an adjuvant to midazolam for sedation of 30 outpatients undergoing upper gastrointestinal endoscopy. The operating conditions and recovery times were compared with those of a similar group of 30 patients sedated with midazolam only. The use of alfentanil resulted in improved operating conditions and a more rapid recovery.

Reversal of infection with Mycobacterium avium intracellulare by treatment with alpha-interferon in a patient with hairy cell leukemia.

A patient with debilitating hairy cell leukemia and documented Mycobacterium avium intracellulare infection unresponsive to standard antituberculous therapy who was treated with alpha-interferon is described. A rapid clinical response with correction of underlying pancytopenia and eradication of the atypical mycobacteria infection was found. No deleterious effects from alpha-interferon therapy were found.

Phase I/II study of recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF) in bone marrow failure.

We performed a Phase I/II study of the administration of recombinant human GM-CSF to patients suffering from severe bone marrow failure, either due to aplastic anemia or myelodysplastic syndrome. Doses ranging from 15 micrograms/m2 to 480 micrograms/m2 were administered as an intravenous infusion daily for 7 days. Temporary improvements were seen in granulocyte counts, monocyte counts and reticulocyte counts.

Phase I/II study of recombinant human granulocyte-macrophage colony-stimulating factor in aplastic anemia and myelodysplastic syndrome.

We performed a phase I/II study of the administration of recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF) to patients with aplastic anemia or myelodysplastic syndrome. Doses ranging from 15 to 480 micrograms/m2 were administered as a one-hour or four-hour intravenous infusion daily for 7 days or as a 12-hour infusion for 14 days. Temporary improvements were seen in granulocyte counts, monocyte counts, and reticulocyte counts in six of eight patients with aplastic anemia and five of seven patients with myelodysplastic syndromes.

Biochemical and thrombolytic properties of a low molecular weight form (comprising Leu144 through Leu411) of recombinant single-chain urokinase-type plasminogen activator.

The cDNA encoding a low Mr derivative (residues 144-411) of human single-chain urokinase-type plasminogen activator was cloned, the recombinant low Mr single-chain urokinase-type plasminogen activator (rscu-PA-32k) was expressed in Chinese hamster ovary cells, and the translation product was purified to homogeneity from conditioned cell culture medium. rscu-PA-32k is very similar to intact recombinant single-chain urokinase-type plasminogen activator in terms of its very low activity (120 IU/mg) on a chromogenic substrate for urokinase (pyroglutamylglycylarginine p-nitroanilide), its plasminogen-dependent fibrinolytic activity on fibrin plates (specific activity = 170,000 IU/mg), its plasminogen activating potential, and the lack of specific binding to fibrin. In a rabbit jugular vein thrombosis model, comparable thrombolysis was obtained with rscu-PA-32k as compared to low molecular weight two-chain urokinase (50% lysis at 2.

Enzymatic properties of single-chain and two-chain forms of a Lys158----Glu158 mutant of urokinase-type plasminogen activator.

Recombinant single-chain urokinase-type plasminogen activator (rscu-PA), in which the plasmin-sensitive peptide bond Lys158-Ile159 is destroyed by site-specific mutagenesis of Lys158 to Glu (rscu-PA-Glu158), is quantitatively converted to two-chain urokinase-type plasminogen activator (rtcu-PA-Glu158) by treatment with endoproteinase Glu-C (Staphylococcus aureus V8 proteinase). The catalytic efficiency (k2/Km) of rscu-PA-Glu158 for the activation of plasminogen is 20 times lower (0.0001 microM-1 s-1) than that of rscu-PA (0.