Both stress response and antidepressant drug action may be mediated by beta-adrenergic receptors (beta AR). Since learned helplessness is a stress-induced animal model of depression, beta AR are relevant to investigate in this model. To date, studies have measured changes in total receptor density (RT), but have not examined more detailed aspects of signal transduction mechanisms such as coupling of the receptor to GS protein. We have investigated brain beta AR coupling in the frontal cortex, hippocampus and hypothalamus of rats exposed to inescapable shock and then tested for learned helplessness, and in both tested and naive controls using [125I]-iodocyanopindolol (ICYP) as the ligand. Both antagonist-saturation and agonist-displacement experiments were conducted, and the specificity for the beta AR was optimized by excluding ICYP binding to 5HT1B receptors. The percentage receptor density in the high-conformational state (%RH) and the ratio of agonist (isoproterenol) dissociation constant from the receptor in the low-/high-conformational states (KL/KH) were used as indices of coupling to GS protein. No significant differences were found between rats developing learned helplessness and non-helpless rats after inescapable stress in any parameter measured in any brain region. In the frontal cortex, exposure to inescapable shock induced beta AR uncoupling from GS protein as suggested by a low KL/KH ratio both in helpless and non-helpless rats but not in either control group. In the hypothalamus, there were trends for higher RL, RT and KL/KH ratio in helpless rats and stressed controls compared to naive controls. These findings suggest that beta AR binding parameters in frontal cortex, hippocampus or hypothalamus did not differentiate between helpless and non-helpless rats. Changes in beta AR coupling observed in these brain regions may reflect effects of stress, which appeared to be region-specific, rather than stress-induced behavioral depression.

Adrenergic beta-Antagonists↗

PubMedDate not supplied

An unusual presentation of Zenker's diverticulum.

Zenker's diverticula are esophageal outpouchings in the region of the cricopharyngeus which typically grow in a posterolateral and inferior direction and can cause esophageal compression if the diverticulum is large enough. We describe a patient in whom a Zenker's diverticulum expanded posteriorly and superiorly so that it was positioned in the posterior pharyngeal space, causing both esophageal and tracheal narrowing.

Aged↗

PubMedDate not supplied

The 90,000 dalton heat shock protein, a lot of smoke but no function as yet.

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Animals↗

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Cotranslational folding of nascent proteins on Escherichia coli ribosomes.

Evidence is presented for cotranslational folding of rhodanese or ricin during its synthesis on Escherichia coli ribosomes. During transcription-translation, full-length but enzymatically inactive polypeptides accumulated as peptidyl-tRNA on the ribosomes. These polypeptides were activated and released by subsequent incubation with the bacterial chaperones and with release factor (RF-2). Coumarin was incorporated cotranslationally at the N-terminus of the nascent protein from fluorophore-S-Ac-Met-tRNAf. Changes in fluorescence indicated that DnaJ bound to the nascent proteins and to a fluorescently labeled synthetic peptide corresponding to the N-terminal 17 amino acids of bovine rhodanese. This peptide also bound to 70S ribosomes or 50S subunits but not to 30S subunits. It inhibited activation and RF-2-dependent release of the full-length ribosome-bound rhodanese. A deletion mutant of rhodanese lacking the N-terminal 23 amino acids was not accumulated on the ribosome but was synthesized very efficiently. However, the protein that was formed was enzymatically inactive. DnaJ did not bind to this deletion mutant on ribosomes. We conclude that the chaperone-mediated reactions facilitate binding of the N-terminal sequence of nascent proteins to a specific site on 50S ribosomal subunits where it blocks release. The ribosome-bound protein undergoes chaperone-mediated reactions that are required for folding into an enzymatically active conformation.

Amino Acid Sequence↗

PubMedDate not supplied

Sequential administration of interferon-gamma, GM-CSF, and interleukin-2 in patients with metastatic renal cell carcinoma: results of a phase II trial.

Various cytokine combinations have been tested for efficacy in the treatment of metastatic renal cell carcinoma (MRCC). Because several immunologic synergisms between granulocyte-macrophage colony-stimulating-factor (GM-CSF) and interleukin-2 (IL-2) have been demonstrated, this phase II trial was conducted on the efficacy and toxicity of subcutaneous, sequentially administered, interferon-gamma (IFNgamma), GM-CSF, and IL-2. Fifty-five consecutive patients with MRCC were treated with 100 microg recombinant IFNgamma1b administered thrice weekly during weeks 1 and 4, followed by 400 microg GM-CSF on 5 consecutive days during weeks 2 and 5. In weeks 3 and 6, patients received 4.5 MU recombinant IL-2 from days 1 to 4. The treatment was repeated every 8 weeks. Five (10%) of patients experienced an objective response (complete response [CR]: 2%, partial response [PR]: 8%). Fourteen (26%) patients had stable disease with a median duration of 19 months (6-47+). The median overall survival was 12 months (range: 0.3-44 months). No toxicity greater than World Health Organization grade II was observed, with fever (43%) and erythema (43%) being the most frequent side effects. Compared with other phase II trials with IFN-gamma and IL-2 alone, the addition of GM-CSF failed to improve response or survival in patients with MRCC.

Adult↗

PubMedDate not supplied

Mental health: living in two worlds.

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Adult↗

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[An unusual cause of subcutaneous postsacral swelling].

A subcutaneous sacrococcygeal located myxopapillary ependymoma is a rare presentation of this malignancy. It has a tendency to metastasize, even after a long latent period. This is a report of such a case together with proposals for treatment and follow-up.

Adolescent↗