Needs and recommendations for behavior research in the prevention and early detection of cancer.

Because life-style patterns affect many cancer risks, research on health-risk behavior and behavior change is critical to cancer prevention. This report recommends priorities for the next decade of psychosocial research on cancer prevention and detection. The leading priority for future research is to fill gaps in basic knowledge left by the rush to intervention and outcome studies.

Processing of Alzheimer beta/A4 amyloid precursor protein: modulation by agents that regulate protein phosphorylation.

The turnover and processing of the Alzheimer beta/A4 amyloid precursor protein (beta APP) has been studied in PC12 cells after treatment with agents that regulate protein phosphorylation. Phorbol 12,13-dibutyrate, an agent that stimulates protein kinase C, decreased the levels of mature beta APP and increased the levels of 15- and 19-kDa peptides. These peptides appeared to be COOH-terminal fragments of beta APP, which arose when phorbol 12,13-dibutyrate increased the rate of proteolytic processing of mature forms of beta APP.

A homozygous transthyretin variant associated with senile systemic amyloidosis: evidence for a late-onset disease of genetic etiology.

Senile systemic amyloidosis (SSA) is a late-onset disease characterized by deposition of amyloid fibrils containing transthyretin (TTR). Amino acid sequencing of protein isolated from the amyloid fibrils of a patient with SSA identified TTR containing a position - 122 isoleucine-for-valine substitution. This change led to the prediction of a genomic G-to-A transition, destroying an MaeIII restriction site.

Monoclonal immunoglobulin deposition disease: light chain and light and heavy chain deposition diseases and their relation to light chain amyloidosis. Clinical features, immunopathology, and molecular analysis.

Monoclonal immunoglobulin deposition occurs in tissues as Congo Red binding fibrils in light chain amyloidosis, as less structured deposits in light chain deposition disease, and as similar but distinct deposits in light and heavy chain deposition disease. The nonamyloid forms were found in 13 patients who had evidence of plasmacytic dyscrasia by the immunohistochemical detection of immunoglobulin light chains of kappa or lambda class (with or without staining for a single heavy chain isotype) and by the absence of amyloid P component in tissue sections that did not show the birefringence characteristic of amyloid after Congo Red staining. All but two of the patients presented with proteinuria with or without azotemia.

A diffuse infiltrative CD8 lymphocytosis syndrome in human immunodeficiency virus (HIV) infection: a host immune response associated with HLA-DR5.

Study Objective: To describe the clinical, immunologic, and immunogenetic features of a diffuse infiltrative lymphocytic disorder resembling Sjögren syndrome in persons infected with human immunodeficiency virus (HIV).

Design: Clinical case study.

Setting: University-affiliated hospitals and outpatient clinics.

In vivo protein phosphorylation in Drosophila mutants defective in learning and memory.

Polypeptides phosphorylated in vivo in Drosophila mutants defective in learning and memory, were characterized by polyacrylamide gel electrophoresis of subcellular fractions obtained by phase partitioning in Triton X-114 [3]. In the mutants turnip, dunce and Shaker, one or more bands at a molecular weight range of 50-80 kDa had altered 32P incorporation. Some of these bands were altered in more than one mutant.

The spectrum of monoclonal immunoglobulin deposition disease associated with immunocytic dyscrasias.

Immunocytic dyscrasias may be manifested by MIDD often presenting with renal manifestations. The diagnosis is established when deposits are shown by immunopathologic methods to contain a single light-chain isotype in patients who have a monoclonal Ig in the serum or urine, altered kappa:lambda ratio in bone marrow, and/or abnormal biosynthesis of Igs in bone marrow cell cultures. The morphologic expressions of deposits are varied: fibrillar in AL, granular and punctate in LCDD, granular or crystalline in LHCDD, and crystalline in type I cryoglobulinemia.

A quantitative model for the kinetics of cAMP-dependent protein kinase (type II) activity. Long-term activation of the kinase and its possible relevance to learning and memory.

Using computer simulation we have modeled the kinetics of cAMP-dependent protein kinase, type II, following transient pulses of cAMP. We show that under the appropriate physiological conditions, the kinase can remain activated 20 min or longer after the cessation of adenylate cyclase activation, in a process we term long-term activation. Long-term activation depends in part on the state of phosphorylation of the regulatory subunit, because phosphorylation of the regulatory subunit regulates the affinity of this subunit for the catalytic subunit.

A Thy-1 negative lymphoma cell variant defective in the formation of glycosyl-phosphatidylinositol membrane protein anchors.

Thy-1 is a glycoprotein present on the membrane of murine cells of the T-lineage. The mature Thy-1 is anchored to the membrane via a glycolipid, phosphatidylinositide. In order to study the regulation of the synthesis and membrane insertion of this protein, the biochemical properties of a Thy-1.

Nonamyloidotic monoclonal immunoglobulin deposits lack amyloid P component.

Deposits in tissues from 13 patients with amyloid, 8 with monoclonal light chain or light and heavy chain deposition disease, and 2 with both amyloid and nonamyloidotic light chain deposits of the same isotype were examined in parallel for the presence of amyloid P component by immunofluorescence and/or immunoperoxidase methods. Amyloid P component was detected in the amyloid but not the nonamyloid deposits, even in the 2 individuals in whom both types of deposits were present, indicating a specific relationship between the amyloid P component and the amyloid fibrils.

Gamma heavy chain disease in man. Genomic sequence reveals two noncontiguous deletions in a single gene.

A genomic clone was isolated from a human lymphoid cell line which synthesized an NH2-terminally deleted gamma 3 heavy chain disease protein. Nucleotide sequence analysis revealed a normal sequence from 310 bp 5' to the initiator ATG through the codon for VH amino acid 14. Amino acid 15 was derived from the codon for the last J4 amino acid.

Restriction fragment analysis confirms the position 33 mutation in transthyretin from an Israeli patient (SKO) with familial amyloidotic polyneuropathy.

Transthyretin isolated from amyloid fibrils from an Israeli patient with Familial Amyloidotic Polyneuropathy was sequenced by two research groups. One laboratory reported a position 49 Thr----Gly substitution, while the other noted a Phe for Ile interchange at amino acid 33. We used a transthyretin cDNA probe to study DNA from this patient by Southern blotting.

A microtiter-based assay for protein kinase activity suitable for the analysis of large numbers of samples, and its application to the study of Drosophila learning mutants.

We have developed a microtiter-based assay for protein kinase activity which depends on the immobilization of substrate proteins to nitrocellulose. The technique makes use of a filtration manifold, allowing as much as a 10-fold increase in efficiency as compared to other protein kinase assays. We have used this assay to measure cAMP-dependent protein kinase (PKA) in Drosophila learning and memory mutants, with exogenous and endogenous substrates.

A double monoclonal IgG1 kappa and IgG2 kappa in a single myeloma patient. Variation in clonal products and therapeutic responses.

Two electrophoretically homogeneous immunoglobulins were detected in the serum of a patient with multiple myeloma. The heavy chains were of different classes (gamma 1 and gamma 2). The light chains of both were kappa, but had different electrophoretic mobilities on polyacrylamide gels.

In vitro protein phosphorylation in head preparations from normal and mutant Drosophila melanogaster.

We have characterized protein phosphorylation in vitro in subcellular fractions from Drosophila melanogaster heads. Optimal conditions for the incorporation of 32P into proteins, and its dependence on ATP, divalent cations, and cyclic nucleotides have been determined, as well as the effect of inhibitors of ATPase, protein phosphatase, and protein kinase on protein phosphorylation. Among these inhibitors, Zn2+ was found to affect the incorporation of 32P into specific bands and p-hydroxymercuribenzoate was found to be most suited for freezing the activity of both kinases and phosphatases.

Oncogene alterations in primary human colon tumors.

We have examined alterations in six oncogenes--H-ras, K-ras, N-ras, myc, fos, and N-myc--in nine primary human colon tumors. Tumors were obtained within an hour of resection; as a control for each tumor, adjacent normal colon tissue was also obtained. Deoxyribonucleic acid extracted from each tissue sample was assayed by digesting with appropriate restriction endonucleases and, after gel electrophoresis and transfer to nitrocellulose, hybridizing with radiolabeled oncogene probes.

Amyloidosis in subcutaneous heroin abusers ("skin poppers' amyloidosis").

Systemic amyloidosis has recently emerged as a major cause of nephropathy among heroin abusers in New York City. Although focal glomerulosclerosis is typically seen in intravenous drug abusers who present with the nephrotic syndrome, those who escape this complication are at risk for the later development of amyloidosis related to their use of the subcutaneous route. Twenty such addicts identified between 1981 and 1984 are described.

Aberrant immunoglobulin synthesis in light chain amyloidosis. Free light chain and light chain fragment production by human bone marrow cells in short-term tissue culture.

Bone marrow cells obtained from 14 patients with light chain amyloid (AL) deposition were examined by biosynthetic labeling techniques. These analyses identified free monoclonal light chain (L-chain) synthesis even in those patients whose serum or urine contained no M protein or free L-chains or only an intact M protein. The experiments also identified a subset of patients whose plasma cells synthesized polypeptides bearing constant region antigenic determinants that migrated more rapidly than intact L-chains on polyacrylamide gels.

Characterization of renal amyloid derived from the variable region of the lambda light chain subgroup II.

Amyloid fibrils were extracted from the kidney of a patient (CHE) shown to have tetramers and dimers of a monoclonal lambda light chain in his serum, and whose bone marrow cells in short-term culture synthesized these forms and a smaller lambda fragment of approximately 10,000 to 12,000 daltons. Biochemical and serologic analysis of a fraction of a size (obtained from amyloid fibrils extracted from the kidney) similar to that synthesized by the bone marrow cells revealed a light chain fragment corresponding to the amino terminal end of the variable region of the lambda light chain subgroup II. The presence of similarly sized short fragments of lambda light chain in both the synthesized and deposited protein suggests that aberrant synthesis and/or proteolytic degradation may play a pathogenetic role in the process of amyloidogenesis.

Lack of class I H-2 antigens in cells transformed by radiation leukemia virus is associated with methylation and rearrangement of H-2 DNA.

Transformation of murine thymocytes by radiation leukemia virus is associated with reduced expression of the class I antigens encoded in the major histocompatibility complex (MHC) and increased methylation and altered restriction enzyme patterns of MHC DNA. These changes may play a role in host susceptibility to virus-induced leukemogenesis and accord with the notion that viral genomes play a regulatory function when they integrate adjacent to histocompatibility genes.

The use of electromyography to quantify muscle pain.

This study was designed to determine the feasibility of using electromyography (EMG) to quantify muscle pain in patients suffering from chronic myofacial pain dysfunction (MPD). Ten patients were carefully selected to include those having mild to severe pain, but not any major psychological or other physiological dysfunction. Measurements of perceived pain and EMG frequency and amplitude were recorded before and after standard analgesic therapy.