Ethanol causes translocation of cAMP-dependent protein kinase catalytic subunit to the nucleus.

Short- and long-term ethanol exposures have been shown to alter cellular levels of cAMP, but little is known about the effects of ethanol on cAMP-dependent protein kinase (PKA). When cAMP levels increase, the catalytic subunit of PKA (C alpha) is released from the regulatory subunit, phosphorylates nearby proteins, and then translocates to the nucleus, where it regulates gene expression. Altered localization of C alpha would have profound effects on multiple cellular functions. Therefore, we investigated whether ethanol alters intracellular localization of C alpha. NG108-15 cells were incubated in the presence or absence of ethanol for as long as 48 h, and localization of PKA subunits was determined by immunocytochemistry. We found that ethanol exposure produced a significant translocation of C alpha from the Golgi area to the nucleus. C alpha remained in the nucleus as long as ethanol was present. There was no effect of ethanol on localization of the type I regulatory subunit of PKA. Ethanol also caused a 43% decrease in the amount of type I regulatory subunit but had no effect on the amount of C alpha as determined by Western blot. These data suggest that ethanol-induced translocation of C alpha to the nucleus may account, in part, for diverse changes in cellular function and gene expression produced by alcohol.

The control of hematopoiesis and leukemia: from basic biology to the clinic.

Hematopoiesis gives rise to blood cells of different lineages throughout normal life. Abnormalities in this developmental program lead to blood cell diseases including leukemia. The establishment of a cell culture system for the clonal development of hematopoietic cells made it possible to discover proteins that regulate cell viability, multiplication and differentiation of different hematopoietic cell lineages, and the molecular basis of normal and abnormal blood cell development. These regulators include cytokines now called colony-stimulating factors (CSFs) and interleukins (ILs). There is a network of cytokine interactions, which has positive regulators such as CSFs and ILs and negative regulators such as transforming growth factor beta and tumor necrosis factor (TNF). This multigene cytokine network provides flexibility depending on which part of the network is activated and allows amplification of response to a particular stimulus. Malignancy can be suppressed in certain types of leukemic cells by inducing differentiation with cytokines that regulate normal hematopoiesis or with other compounds that use alternative differentiation pathways. This created the basis for the clinical use of differentiation therapy. The suppression of malignancy by inducing differentiation can bypass genetic abnormalities that give rise to malignancy. Different CSFs and ILs suppress programmed cell death (apoptosis) and induce cell multiplication and differentiation, and these processes of development are separately regulated. The same cytokines suppress apoptosis in normal and leukemic cells, including apoptosis induced by irradiation and cytotoxic cancer chemotherapeutic compounds. An excess of cytokines can increase leukemic cell resistance to cytotoxic therapy. The tumor suppressor gene wild-type p53 induces apoptosis that can also be suppressed by cytokines. The oncogene mutant p53 suppresses apoptosis. Hematopoietic cytokines such as granulocyte CSF are now used clinically to correct defects in hematopoiesis, including repair of chemotherapy-associated suppression of normal hematopoiesis in cancer patients, stimulation of normal granulocyte development in patients with infantile congenital agranulocytosis, and increase of hematopoietic precursors for blood cell transplantation. Treatments that decrease the level of apoptosis-suppressing cytokines and downregulate expression of mutant p53 and other apoptosis suppressing genes in cancer cells could improve cytotoxic cancer therapy. The basic studies on hematopoiesis and leukemia have thus provided new approaches to therapy.

On the belief that arthritis pain is related to the weather.

There is a widespread and strongly held belief that arthritis pain is influenced by the weather; however, scientific studies have found no consistent association. We hypothesize that this belief results, in part at least, from people's tendency to perceive patterns where none exist. We studied patients (n = 18) for more than I year and found no statistically significant associations between their arthritis pain and the weather conditions implicated by each individual. We also found that college students (n = 97) tend to perceive correlations between uncorrelated random sequences. This departure of people's intuitive notion of association from the statistical concept of association, we suggest, contributes to the belief that arthritis pain is influenced by the weather.

The University of Alicante Library copy of Palmerin d'Oliva (London, 1637): A Bibliographical Description

The purpose of this article is to provide bibliographical information about a copy of the fourth edition of the two parts of Anthony Munday's translation of Palmerin d'Oliva (London, 1637; STC 19160) recently purchased by the University of Alicante Library and not mentioned in the standard bibliographies. The article contains a detailed bibliographical description based on Bowers's principles (1949) and is designed to be useful to scholars by making direct consultation of the copy in most cases unnecessary. The description is preceded by a short introduction to the literary text and its publication in England.

The medical genius ; a guide to the cure /

Mode of access: Internet.

Economic study of Puerto Rico : report to the President /

Includes bibliographies.

Immigration reform : status of implementing employer sanctions after one year : report to the Congress /

"B-125051"--P. [1]

Puerto Rico's political future : a divisive issue with many dimensions : report to the Congress /

"B-193013"--Prelim. p.

The Covenanters, a history of the church in Scotland from the Reformation to the Revolution,

Mode of access: Internet.

Costs and problems of completing the interstate highway system; report to the Congress.

Mode of access: Internet.

Safety standards on small passenger aircraft - with nine or fewer seats - are significantly less stringent than on larger aircraft. Comptroller General's report to the Congress.

Mode of access: Internet.

The third U.N. Law of the Sea Conference : report to the Senate /

At head of title: 94th Congress, 1st session. Committee print.

The Third U.N. Law of the Sea Conference, Geneva Session, March-May 1975 [microform] : report to the Senate /

Reuse of record except for individual research requires license from Congressional Information Service, Inc.

El Salvador at war : an oral history of conflict from the 1979 insurrection to the present /

Mode of access: Internet.

Annual report of the Board of Directors of the Panama Rail Road Company to the stockholders.

Mode of access: Internet.