A clinical and immunologic study of employees in a facility manufacturing trimellitic anhydride.

We conducted a 1-year cross-sectional survey of 474 employees of a large chemical manufacturing complex to relate trimellitic anhydride (TMA) exposure to serologic and clinical outcomes. In 1988-1989, employees were evaluated by history and immunologic assay of total (T) and IgE antibody to trimellityl human serum albumin (TM-HSA). All employees were assigned to a TMA exposure class, from 1 (highest) to 5 (lowest), by an industrial hygienist, independent of the clinical and immunological data. Thirty-two (6.8%) of 474 employees had a TMA immunologic syndrome, 31.6% with an irritant response and 61.6% with no symptoms. Twelve had asthma/rhinitis, 10 had the late respiratory systemic syndrome (LRSS), four had late onset asthma, one had late onset arthralgia, and five had a distant history of LRSS. Included in this survey of the entire work force were 321 new enrollees, who had not joined the previous (1976 to 1988) voluntary surveillance program. Only four (1.3%) of the new enrollee group had a TMA immunologic syndrome. Among new enrollees, there were lower mean total and IgE serum antibody levels in lower exposure classes and a higher percentage with elevated antibody levels in high exposure classes (for T, x2 = 17.5, p = .0016; for IgE, x2 = 76.7, p less than .0001). In the new enrollee population, demographic variables of age, sex, date of hire, and smoking status were examined related to antibody levels. Only current or former smoking was related to elevated total antibody levels.


Cyclin-B homologs in Saccharomyces cerevisiae function in S phase and in G2.

We have cloned four cyclin-B homologs from Saccharomyces cerevisiae, CLB1-CLB4, using the polymerase chain reaction and low stringency hybridization approaches. These genes form two classes based on sequence relatedness: CLB1 and CLB2 show highest homology to the Schizosaccharomyces pombe cyclin-B homolog cdc13 involved in the initiation of mitosis, whereas CLB3 and CLB4 are more highly related to the S. pombe cyclin-B homolog cig1, which appears to play a role in G1 or S phase. CLB1 and CLB2 mRNA levels peak late in the cell cycle, whereas CLB3 and CLB4 are expressed earlier in the cell cycle but peak later than the G1-specific cyclin, CLN1. Analysis of null mutations suggested that the CLB genes exhibit some degree of redundancy, but clb1,2 and clb2,3 cells were inviable. Using clb1,2,3,4 cells rescued by conditional overproduction of CLB1, we showed that the CLB genes perform an essential role at the G2/M-phase transition, and also a role in S phase. CLB genes also appear to share a role in the assembly and maintenance of the mitotic spindle. Taken together, these analyses suggest that CLB1 and CLB2 are crucial for mitotic induction, whereas CLB3 and CLB4 might participate additionally in DNA replication and spindle assembly.


Fission yeast genes involved in coupling mitosis to completion of DNA replication.

We have isolated fission yeast mutants that enter mitosis when DNA replication is blocked with hydroxyurea. The mutants define eight linkage groups, three of which consist of alleles of the rad1, rad3, and rad17 genes. Recently, these fission yeast genes have been shown to be required for radiation-induced cell cycle arrest, as is the budding yeast RAD9 gene. The other five genes are called hus (hydroxyurea sensitive) 1-5. We propose that these genes participate in an intracellular signal transduction pathway that monitors the completion of DNA replication and transmits information to the mitotic control protein cdc2. Mutations that bypass the requirement for cdc25 (an activator of the mitotic regulator cdc2) also uncouple mitosis from DNA replication. However, mitosis is blocked by inhibitors of DNA replication in strains in which the cdc25 gene has been deleted, indicating that although cdc25 influences the coupling of mitosis to the completion of DNA replication, it is not essential for this control.


Interaction of HTLV-1 Tax1 with p67SRF causes the aberrant induction of cellular immediate early genes through CArG boxes.

Tax1 of human T-cell leukemia virus type 1 (HTLV-1) is a transcriptional activator for viral gene expression and is also a transforming protein through inducing the expression of several cellular genes under the control of mitogenic signals. We identified the CArG boxes as a Tax1-responsive cis-acting element for the cellular immediate early genes c-fos, egr-1, and egr-2. Using a chimeric protein consisting of the CArG-binding factor p67SRF and the heterologous DNA-binding domain of a yeast transcription factor GAL4, we demonstrated that Tax1 activates the transcriptional activity of p67SRF through the GAL4-binding site. The carboxy-terminal half of p67SRF, which lacks domains for DNA-binding, dimerization, and ternary complex formation with p62TCF, was sufficient for the activation by Tax1. Tax1 produced in Escherichia coli bound p67SRF in vitro. The complex formation in vivo was also indicated by the finding that the acidic activation domain of VP16, by fusion to p67SRF, can complement the transcriptional activation function of a mutant Tax1 in trans. Thus, Tax1 activates CArG-mediated transcription without mitogenic signals through interaction with a CArG-binding factor, p67SRF. This must be one of the primary steps by which Tax1 causes aberration in growth control of the infected cells.


The VP16 transcription activation domain is functional when targeted to a promoter-proximal RNA sequence.

Among eukaryotic transcription trans-activators, the human immunodeficiency virus type 1 (HIV-1) Tat protein is exceptional in that its target site TAR is an RNA rather than a DNA sequence. Here, we confirm that fusion of Tat to the RNA-binding domain of the HIV-1 Rev protein permits the efficient activation of an HIV-1 long terminal repeat (LTR) promoter in which critical TAR sequences have been replaced by RNA sequences derived from the HIV-1 Rev response element (RRE). An RRE target sequence as small as 13 nucleotides is shown to form an effective in vivo target for Rev binding. More important, a fusion protein consisting of Rev attached to the VP16 transcription activation domain was also observed to efficiently activate the HIV-1 LTR from this nascent RNA target. These data demonstrate that trans-activation of transcription by acidic activation domains does not require a stable interaction with the promoter DNA and suggest that VP16, like Tat, can act on steps subsequent to the formation of the HIV-1 LTR preinitiation complex. The finding that the activation domains of VP16 and Tat are functionally interchangeable raises the possibility that these apparently disparate viral trans-activators may nevertheless act via similar mechanisms.


Mutations affecting stability and deadenylation of the yeast MFA2 transcript.

Decay rates of individual mRNAs in the yeast Saccharomyces cerevisiae can vary by 10- to 20-fold. To determine the basis for the rapid degradation of the mRNA encoded by the yeast MFA2 gene we have used a genetic screen to isolate mutations that increase the stability of this transcript. Analysis of point mutations obtained from this screen, and of additional lesions constructed in vitro, indicated that the MFA2 3'-untranslated region (UTR) contains sequences that specify rapid mRNA decay. Moreover, the lesions that affected mRNA decay rate also affected the process of mRNA deadenylation. Mutations in one region of the 3' UTR both decreased the rate of poly(A) shortening and increased the stability of an intermediate form in the decay pathway with an oligo(A) tail (approximately 10 nucleotides). Mutations in a second region primarily increased the stability of the oligo(A) form. These results suggest that the decay of the MFA2 mRNA initiates with the shortening of the poly(A) tail and there are specific sequences within the 3' UTR that stimulate poly(A) tail shortening as well as subsequent steps in the decay pathway. Given the similarity of this decay pathway to that seen for some mammalian mRNAs, these results suggest that mRNA deadenylation may be a common mechanism of mRNA turnover.


An essential splicing factor, SLU7, mediates 3' splice site choice in yeast.

Recently, we have reported the identification of several genes that exhibit genetic interactions with the U5 snRNA. Two of these genes, SLU4 and SLU7 (SLU: synergistic lethal with U5 snRNA), encode products required for the second catalytic step of splicing. To analyze the specific roles of SLU4 and SLU7, we have determined how mutants influence the relative usage of competing 3' splice sites. We find that mutations in SLU7 eliminate the normal 20-fold preference for 3' splice sites located > 22 nucleotides downstream of the branchpoint. In contrast, mutations in SLU4 inhibit usage of all 3' splice sites, regardless of their location. This suggests that SLU7 is involved in the process of 3' splice site choice, whereas SLU4 fulfills a generic requirement for the second step. We show that SLU7 is an essential gene that contains a small motif with striking similarity to the cysteine-rich zinc knuckle of retroviral nucleocapsid proteins, which has been implicated in RNA binding. Mutational analysis of SLU7 indicates that this motif influences the efficiency, but not the sequence specificity, of 3' splice site selection. The identification of a component of the constitutive splicing machinery that can promote 3' splice site choice has potentially important implications for alternative splicing.


The Drosophila couch potato protein is expressed in nuclei of peripheral neuronal precursors and shows homology to RNA-binding proteins.

Through enhancer detection screens we have isolated and cloned an essential gene that is expressed in the neuronal precursors and their daughter cells in the Drosophila embryonic peripheral nervous system (PNS). The gene is named couch potato (cpo), because several partial loss-of-function alleles cause hypoactive behavior in adults. Here, we present evidence that the structure of the cpo locus is unusually complex: It spans > 100 kb, encodes three different messages, is differentially spliced, lacks an AUG initiation codon, and may encode three different proteins. Two putative Cpo proteins contain similar but nonidentical RNA-binding domains that are most homologous to the RNA-binding domains of the Drosophila embryonic lethal abnormal vision (elav) gene and a human brain protein that has been implicated in a paraneoplastic sensory neuropathy. Polyclonal antibodies raised against a fusion protein localize Cpo to the nucleus. Immunocytochemical studies demonstrate that the achaete-scute and daughterless genes are required for proper expression of cpo in the PNS but not in other cells that express cpo. On the basis of our observations, we present a model in which cpo is controlled by genes that determine cells to become PNS cells. Cpo, in turn, may control the processing of RNA molecules required for the proper functioning of the PNS.


deadpan, an essential pan-neural gene in Drosophila, encodes a helix-loop-helix protein similar to the hairy gene product.

Neural precursor cells in Drosophila acquire their identity early during their formation. In an attempt to determine whether all neural precursors share a set of genetic machinery, perhaps to control properties of differentiation common to all neurons, we used the enhancer-trap method to identify several genes (pan-neural genes) that are expressed in all neurons and/or their precursors. One of the pan-neural genes is deadpan, which encodes a helix-loop-helix protein closely related to the product of the segmentation gene hairy. The function of deadpan is essential for viability and is likely to be involved in the functional rather than the morphological differentiation of neurons.


Allelic diversity of the maize B regulatory gene: different leader and promoter sequences of two B alleles determine distinct tissue specificities of anthocyanin production.

The B gene encodes a transcription factor of the basic helix-loop-helix class, which controls the synthesis of the anthocyanin pigments in maize. This gene, as well as the highly homologous R gene family, displays extensive allelic variation in that different alleles cause distinct distributions of anthocyanin pigments in different tissues and at different developmental times. The analysis of the expression of two B alleles, with distinct tissue-specific patterns of anthocyanin synthesis in plant and seed tissues, demonstrates that the amount of B transcripts correlates with the accumulation of anthocyanins in the various tissues. The comparison of the genomic clones for the two alleles reveals high sequence identity in the coding and 3'-flanking regions (98% and approximately 90%, respectively). In contrast, the most 5' region of their mRNAs and the 5'-flanking sequences share no significant sequence identity. This result suggests that the alleles diverged from each other by complex genome rearrangements rather than by simple base pair substitutions. We have used the high velocity microprojectile transformation assay to demonstrate that the differential expression of the two alleles in the seed is determined by their 5' variant sequences. Thus, the variation in tissue-specific anthocyanin synthesis in plants with these different B alleles is controlled at the level of B gene expression.


Promoter melting and TFIID complexes on Drosophila genes in vivo.

In vivo UV cross-linking and nuclear transcriptional run-on experiments have shown that a number of Drosophila genes possess an elongationally paused RNA polymerase on their 5' ends. Here, we examine in vivo promoters that do and do not possess paused polymerases using the single-stranded DNA-probing reagent KMnO4. Melted DNA helices are found associated with the pause site of the uninduced hsp70 and hsp26 heat shock genes and the constitutively expressed beta-1 tubulin gene. The histone H1 and H2B genes, which lack a paused polymerase, have no comparable region of melted DNA. Melting at the pause site persists upon heat shock induction of the hsp70 and hsp26 genes, indicating that pausing continues after gene activation. Interestingly, activation triggers additional melting, both at the start site (in the region where open complexes would be expected to form) and downstream of the uninduced pause site. In the course of our studies, we discovered that some T residues of the TATA box were protected from KMnO4 modification in both induced and uninduced cells. This protection appears to be a consequence of TFIID binding, as a similar protection pattern could be produced in vitro with purified protein.


The block to transcriptional elongation within the human c-myc gene is determined in the promoter-proximal region.

A conditional block to transcriptional elongation is an important mechanism for regulating c-myc gene expression. This elongation block within the first c-myc exon was defined originally in mammalian cells by nuclear run-on transcription analyses. Subsequent oocyte injection and in vitro transcription analyses suggested that sequences near the end of the first c-myc exon are sites of attenuation and/or premature termination. We report here that the mapping of single stranded DNA in vivo with potassium permanganate (KMnO4) and nuclear run-on transcription assays reveal that polymerase is paused near position +30 relative to the major c-myc transcription initiation site. Deletion of 350 bp, including the sites of 3'-end formation and intrinsic termination defined in oocyte injection and in vitro transcription assays does not affect-the pausing of polymerase in the promoter-proximal region. In addition, sequences upstream of +47 are sufficient to confer the promoter-proximal pausing of polymerases and to generate the polarity of transcription farther downstream. Thus, the promoter-proximal pausing of RNA polymerase II complexes accounts for the block to elongation within the c-myc gene in mammalian cells. We speculate that modification of polymerase complexes at the promoter-proximal pause site may determine whether polymerases can read through intrinsic sites of termination farther downstream.


Escherichia coli RuvA and RuvB proteins specifically interact with Holliday junctions and promote branch migration.

The Escherichia coli ruvA and ruvB genes are involved in DNA repair and in the late step of homologous genetic recombination. We have demonstrated previously that the RuvA-RuvB protein complex in the presence of ATP promotes reabsorption of cruciform structures extruded from a supercoiled plasmid with an inverted repeat sequence. Because the cruciform structure is topologically analogous to the Holiday structure, we have proposed that the role of the RuvA and RuvB proteins in recombination is to promote a strand exchange reaction at the Holliday junction. Here, we studied the specific interaction of the RuvA-RuvB complex with the Holliday structure using synthetic analogs prepared by annealing four oligonucleotides. The affinities of the RuvA protein for synthetic Holliday junctions are much higher (> 20-fold) than for duplex DNA, and the affinities of the RuvA protein for the junctions are further enhanced (> 4-fold) by the interaction with the RuvB protein. The RuvA-RuvB protein complex in the presence of ATP promotes dissociation of the synthetic Holliday junction with homology in the central core into two halves by catalyzing branch migration to the DNA ends, but it does not affect the structure of the synthetic Holliday junction without the homology. The separation of the synthetic Holliday junction is a result of the activity of the RuvA-RuvB complex that promotes strand exchange and DNA unwinding. Furthermore, RuvA and RuvB promote the strand exchange reaction at the Holliday junctions made by RecA. These results provide further evidence that the RuvA-RuvB complex recognizes the Holliday junction and promotes branch migration in homologous recombination.


Cloning, sequencing, overproduction, and purification of M. CviBI (GANTC) methyltransferase from Chlorella virus NC-1A [corrected].

We have cloned and sequenced the cvibIM gene from Chlorella virus NC-1A by selecting for the modification phenotype. The modification gene was cloned on a 7-kb BamHI fragment inserted into the BamHI site of the pUC13 plasmid. The cvibIM gene was localized at the 3' end of this fragment. Sequencing of this region revealed a large open reading frame that codes for methyltransferase (MTase; symbol M.) (predicting 260 amino acids). M.CviBI (GANTC) aa sequence is homologous to M.Dam(GATC), M.DpnII(GATC), and M.T4 (GATC), and not so to M.HinfI(GANTC), M.HhaII (GANTC), and M.DpnA(GATC). We also describe the use of the polymerase chain reaction technique to alter transcriptional and translational signals surrounding this gene so as to achieve overexpression in Escherichia coli. This construct yields M.CviBI at 2-3% of the total cellular protein. The MTase was purified by phosphocellulose, DEAE, and gel filtration chromatography. Its size by SDS-PAGE is approx. 28 kDa, in good agreement with that predicted from the nucleotide sequence.


Protein-coding introns from the 23S rRNA-encoding gene form stable circles in the hyperthermophilic archaeon Pyrobaculum organotrophum.

Two archaeal introns have been discovered in the single-copy 23S rRNA-encoding gene of the hyperthermophile, Pyrobaculum organotrophum. After excision from rRNA transcripts, both introns circularize and are stably retained in the cell. Putative proteins encoded by the introns and covering most of the intron sequence share a decapeptide motif with proteins encoded by another archaeal intron and by group I introns.


Amino acid substitution in the C-terminal arm domain of HU-2 results in an enhanced affinity for DNA.

Three mutants of the Escherichia coli hupA gene, encoding the HU-2 protein, were constructed by synthetic oligodeoxyribonucleotide-directed, site-specific mutagenesis on M13mp18 vectors. The resulting HupAN10, HupAN11 and HupAN12 proteins contained Thr59-->Lys, Gln64-->Lys and Asn53-->Arg substitutions, respectively. These amino acid (aa) changes increased the positive charge of the N-terminal half of the two-strand, antiparallel beta-ribbon of the arm structure, which is believed to be a domain for DNA binding. The three mutant proteins bound to DNA more tightly than wild-type HU-2, and their affinities for DNA increased in the order of HupAN10, HupAN11, HupAN12. The mutant proteins showed a slightly increased HU activity for supporting Mu phage development. A mutant HU-2 protein with increased basicity, but with an altered aa sequence in the arm region due to a frameshift mutation, was also constructed. This mutant protein showed a reduced affinity to DNA and was unable to support Mu growth, suggesting that a unique aa sequence of the arm domain, rather than mere basicity of this domain, is required for efficient binding to DNA.


Cloning and characterization of genes involved in the biosynthesis of delta-aminolevulinic acid in Escherichia coli.

Several mutants of Escherichia coli that had lost their ability to synthesize delta-aminolevulinic acid (ALA) via the C5 pathway were isolated. Their defective loci were classified into two groups, AlaA- and AlaB-. The genes that complemented these mutations were cloned. Nucleotide sequencing indicated that the gene that complemented AlaA- was identical to hemL which is located at 4 min on the E. coli chromosome and encodes glutamate 1-semialdehyde aminotransferase. The gene complementing AlaB- contained an open reading frame (ORF) encoding a polypeptide of 207 amino acids that was found to be a new gene involved in the synthesis of ALA via the C5 pathway. Thus, we designated the gene hemM. The hemM gene was adjacent to hemA that is located at 27 min and previously thought to encode glutamyl-tRNA dehydrogenase. However, we found that hemA complemented both the AlaA- (hemL) and AlaB- (hemM) mutants defective in the C5 pathway although the transformants showed small colonies on the selective medium without ALA. These results suggest that hemA is not involved in the C5 pathway, but controls a second, minor pathway for the synthesis of ALA.


Molecular analysis of the recA gene of Agrobacterium tumefaciens C58.

The complete nucleotide sequence of the Agrobacterium tumefaciens recA gene was determined. A comparison of the translated open reading frame of the gene with other known recA sequences revealed significant sequence conservation. However, unlike its Escherichia coli equivalent, A. tumefaciens recA lacks the upstream 'SOS box', suggesting a different mechanism of regulation for this gene.


A novel Bacillus subtilis expression vector based on bacteriophage phi 105.

We have developed a novel expression vector based on the bacteriophage phi 105, and employed it for the production of mutant beta-lactamases in Bacillus subtilis. Expression of the beta-lactamase-encoding gene was low when cloned into the prophage under the control of its own promoter. However, expression was considerably elevated when the gene was inserted into the phage genome in the same orientation as phage transcription. A defective phi 105 vector was constructed with a deletion removing a region needed for cell lysis, and with a mutation in the immunity repressor, rendering it temperature sensitive. Production of beta-lactamase could then be induced by a shift in temperature and without concomitant cell lysis, facilitating purification of the protein from the culture supernatant. This phage has considerable potential for development as a vector for controllable production of heterologous proteins in B. subtilis.


Streptomyces lividans glycosylates an exoglucanase (Cex) from Cellulomonas fimi.

Exoglucanase Cex from Cellulomonas fimi is a glycoprotein [Langsford et al., J. Gen. Microbiol. 130 (1984) 1367-1376]. Cex produced by Streptomyces lividans from the cloned cex gene is also glycosylated. The extent and nature of glycosylation are similar for Cex from both organisms. The glycosylation affords protection against proteolysis for the enzymes from both organisms when they are bound to cellulose, but not in solution. The ability to glycosylate cloned gene products enhances the utility of Streptomyces as a host for the production of heterologous polypeptides.


Isolation and characterization of the gene coding for the major sigma factor of Rickettsia prowazekii DNA-dependent RNA polymerase.

The gene coding for the major sigma factor of Rickettsia prowazekii, an obligate intracellular parasitic bacterium, has been isolated utilizing an oligodeoxyribonucleotide as a probe to a conserved region of major sigma factors. Nucleotide sequence analysis revealed an open reading frame of 1905 bp that could encode a protein of 635 amino acids (aa) with a calculated molecular size of 73 kDa (sigma 73). R. prowazekii sigma 73 displayed extensive homology with major sigma factors from a variety of eubacteria. Comparison of the major sigma factors from Escherichia coli and R. prowazekii revealed 44.9% aa identity. R. prowazekii sigma 73 produced in E. coli minicells migrated as a 85-kDa protein when analyzed by sodium dodecyl sulfate-polyacrylamide-gel electrophoresis. This anomalous migration is characteristic of eubacterial major sigma factors and agrees with the migration noted for the purified rickettsial sigma protein. Despite a similarity to the E. coli sigma 70 encoded by rpoD, R. prowazekii sigma 73 did not complement E. coli rpoD temperature-sensitive mutants.


Automatic elimination of unnecessary bacterial sequences from yeast vectors.

Most vectors for Saccharomyces cerevisiae are shuttle vectors which can be both propagated and selected in Escherichia coli. The DNA segments, however, which are required for propagation in E. coli are unnecessary and moreover toxic in S. cerevisiae. To delete these harmful DNA fragments from the vector after it is introduced into S. cerevisiae cells, we propose a specific gene conversion mechanism of a yeast plasmid, pSR1. Plasmid pSR1 has a pair of inverted repeats (IRs) that divides the plasmid molecule into two unique regions. Intramolecular recombination frequently occurs at a pair of specific recombination sites in IRs catalyzed by recombinase R, encoded by a pSR1 plasmid gene. This R-mediated recombination is often accompanied by gene conversion in IRs. Thus, a 2.1-kb pBR322 sequence for the E. coli host ligated into one of the IRs of a composite plasmid was automatically and effectively eliminated when the plasmid was introduced into S. cerevisiae cells.


The phenotype of a dihydrofolate reductase mutant of Saccharomyces cerevisiae.

We have constructed a dihydrofolate reductase mutant (dfr1) of Saccharomyces cerevisiae. The mutant has auxotrophic growth requirements for the C1 metabolites dTMP, adenine, histidine and methionine, similar to those of wild-type (wt) strains grown in the presence of methotrexate (MTX). However, unlike wt strains treated with MTX, the growth requirements of the dfr1 mutant are not satisfied by exogenous 5-formyltetrahydrofolic acid (FA; folinic acid) in complex (YEPD) medium. This result is surprising, as yeast cells treated with MTX are expected to be phenocopies of dfr1 mutants. The inability of the mutants to metabolize FA suggests that the DFR1 gene product may have a role in folate metabolism in addition to its well-characterized function in the reduction of dihydrofolate. From dfr1 strains, we have isolated secondary mutants whose growth can be supported by FA in YEPD medium. This FA-utilizing phenotype is attributable to recessive mutations which we have designated fou. In addition to their inability to metabolize FA, the dfr1 strains are unable to grow on medium containing the non-fermentable carbon source glycerol, suggesting that the DFR1 gene product is also required for mitochondrial function. In order to overcome this lack of respiratory activity in the dfr1 mutants, we isolated strains containing a dominant mutation, DIR, which allows growth on glycerol in the presence of antifolate drugs. When crossed into dfr1 strains, the DIR mutation conferred respiratory competence. These strains should be useful in a variety of studies on the genetics and biochemistry of folate metabolism in this simple eukaryote.


A simple and efficient method for the oligodeoxyribonucleotide-directed mutagenesis of double-stranded plasmid DNA.

A method for the oligodeoxyribonucleotide-directed mutagenesis of double-stranded DNA without the necessity for phenotypic selection is described. Plasmids denatured with alkali and purified by adsorption to and elution from nitrocellulose have single-stranded regions where primers can hybridize and serve as templates for a T7 DNA polymerase-catalyzed synthesis of complementary mutant DNA strands. When this procedure was carried out such that the original nonmutant strand contained uracil [method of Kunkel, Proc. Natl. Acad. Sci. USA 82(1985)488-492], mutation frequencies of between 30% and 40% were obtained. The technique has been used to generate mutant genes in plasmids of a wide variety of sizes. The largest plasmid manipulated and successfully mutagenized was 22 kb. The method is rapid and efficient and is not dependent upon either f1 phage vectors or the presence of restriction sites in the vicinity of the sequence targeted for mutation.


The carboxypeptidase Y-encoding gene from Candida albicans and its transcription during yeast-to-hyphae conversion.

We have cloned and sequenced the gene (CPY1) encoding the carboxypeptidase Y (CPY) of Candida albicans. The gene contains an open reading frame comprising 542 amino acids (aa) with an M(r) of 61,104. The aa sequence shows 74% identity to the mature CPY aa sequence from Saccharomyces cerevisiae. The putative pre (signal) and pro sequences at the N terminus of the C. albicans protein, however, show significant divergence from the corresponding prepro sequence of the S. cerevisiae protein. Southern analysis of C. albicans genomic DNA suggested the presence of only one CPY-encoding gene. Northern analysis during yeast-to-hyphae conversion suggested that the CPY1 gene is transiently down-regulated on a transcriptional level during the early events of this developmental switch.


A vector, pSHT, for the expression and secretion of protein domains in mammalian cells.

A phagemid (pSHT) containing the pUC and M13 ori sequences was constructed to facilitate the expression of partial cDNAs or of sequences encoding mammalian membrane- and secretory-protein domains. It provides a start codon and signal sequence flanked upstream by the simian virus 40 and bacteriophage T7 promoters and downstream by cloning sites, stop codons in all three frames, splicing and polyadenylation signals.


Protein A fusion vectors for use in combination with pEX vectors in the production and affinity purification of specific antibodies.

New vectors expressing protein A fusions were constructed, based upon the kanamycin-resistance-encoding plasmid, pK19. They were designed for use in combination with the pEX series of beta-galactosidase protein-fusion vectors in the production and affinity purification of specific antibodies.


Characterization of the spontaneous elimination of streptomycin sensitivity (SmS) on high-copy-number plasmids: SmS-enforcement cloning vectors with a synthetic rpsL gene.

The strAS or rpsL+ gene, encoding a ribosomal protein, S12, expresses its streptomycin-sensitivity (SmS) phenotype dominantly over strAR or rpsL- gene. Therefore, strAR cells that harbor plasmids with strAS alleles are phenotypically SmS. It was found that the SmS phenotype is unstable, and such cells eventually switch to the Sm-resistance (SmR) phenotype, especially when the strAS gene was cloned on high-copy-number (HCN) plasmids. It seemed that the strA gene cloned on HCN plasmids was toxic to Escherichia coli host cells and, during prolonged cultivation, plasmids with an inactivated strAS gene, mostly carrying insertion sequence elements, such as IS1, IS5 and gamma delta, were selected. The instability of the strA gene was particularly enhanced when the Val51 residue in the middle of S12 protein was replaced by Leu, suggesting enhanced toxicity of the altered S12. Since the strAS gene was stably maintained throughout approx. 100 cell doublings when its expression was abolished, most probably it is the gene product rather than the nucleotide sequence itself that is responsible for the instability of strA gene on HCN plasmids. To improve the stability of the SmS phenotype, the previously reported ampicillin-resistance-conferring and SmS-enforcing plasmid vector, pHSG670, was reconstructed. The resulting vector, pHSG683, confers chloramphenicol resistance, enforces SmS on strAR and supE- host bacteria, and has multiple cloning sites within the coding region of synthetic rpsL gene. When pHSG683 DNA was prepared from strAR and sup+ cells grown in tryptophan-rich medium with Cm and Sm, less than 10(-6) plasmids failed to enforce SmS on strAR and supE- cells in tryptophan-less medium with Cm.(ABSTRACT TRUNCATED AT 250 WORDS)


Synthesis and secretion of an Erwinia chrysanthemi pectate lyase in Saccharomyces cerevisiae regulated by different combinations of bacterial and yeast promoter and signal sequences.

Nine different expression-secretion cassettes, comprising novel combinations of yeast and bacterial gene promoters and secretion signal sequences, were constructed and evaluated. A pectate lyase-encoding gene (pelE) from Erwinia chrysanthemi was inserted between each one of these expression-secretion cassettes and a yeast gene terminator, generating recombinant yeast-integrating shuttle plasmids pAMS1 through pAMS9. These YIp5-derived plasmids were transformed and stably integrated into the genome of a laboratory strain of Saccharomyces cerevisiae, and the pectate lyase production was monitored. Transcription initiation signals for pelE expression were derived from the yeast alcohol dehydrogenase (ADC1P), the yeast mating pheromone alpha-factor (MF alpha 1P) and the Bacillus amyloliquefaciens alpha-amylase (AMYP) gene promoters. The transcription termination signals were derived from the yeast tryptophan synthase gene terminator (TRP5T). Secretion of pectate lyase (PLe) was directed by the signal sequences of the yeast mating pheromone alpha-factor (MF alpha 1S), B. amyloliquefaciens alpha-amylase (AMYS) and Er. chrysanthemi pectate lyase (pelES). The ADC1P-MF alpha 1S expression-secretion system proved to be the most efficient control cassette for the expression of pelE and the secretion of PLe in S. cerevisiae.


Sequence of a cluster of genes controlling synthesis and secretion of alkaline protease in Pseudomonas aeruginosa: relationships to other secretory pathways.

A genetic locus implicated in the synthesis and secretion of alkaline protease (APR) in Pseudomonas aeruginosa has been previously described [Guzzo et al., J. Bacteriol. 172 (1990) 942-948]. The nucleotide sequence of the DNA fragment encoding these functions was determined and revealed the existence of five open reading frames: aprA, the structural gene encoding APR; aprI, which encodes a protease inhibitor; and aprD, aprE, aprF whose products are involved in protease secretion. The AprD, AprE and AprF proteins share significant homology with proteins implicated in secretion of Erwinia chrysanthemi proteases and Escherichia coli alpha-haemolysin. These results provide further evidence for the existence of a specialized secretory system widespread among Gram- bacteria.


Genetic suppression analysis of sigma E interaction with three promoters in sporulating Bacillus subtilis.

Genetic evidence suggests that the sigma (sigma) subunit of RNA polymerase determines the specificity of promoter utilization, by making sequence-specific contacts with DNA. We examined the effects of two single amino acid(aa) substitutions in sigma E on the utilization of mutated derivatives of three different promoters in sporulating Bacillus subtilis. We found allele-specific suppression of mutations in all three promoters by each aa substitution in sigma E. These results provide strong evidence that sigma E interacts with each of these promoters in vivo. Moreover, the specificity of suppression of the mutations by the aa substitutions in sigma E lead us to speculate that the Met124 of sigma E closely contacts two adjacent bp in the -10 region of the promoters.


Cloning, sequencing and expression in Escherichia coli of the ptsI gene encoding enzyme I of the phosphoenolpyruvate:sugar phosphotransferase transport system from Streptococcus salivarius.

We present the cloning and sequencing of the ptsI gene, encoding enzyme I (EI) of the phosphoenolpyruvate (PEP): sugar phosphotransferase (PTS) transport system from Streptococcus salivarius. The ptsI gene corresponds to an open reading frame of 1731 nucleotides, which translates into a putative 577-amino acid (aa) protein with a M(r) of 62,948 and a pI of 4.49. The EI was produced in Escherichia coli under the control of its own promoter located immediately upstream of ptsI, a situation never previously reported for any other gene coding for an EI. The deduced aa sequence of the S. salivarius EI shows a high degree of similarity with the E. coli EI and the EI moiety of the multiphosphoryl transfer protein from Rhodobacter capsulatus. The S. salivarius EI also shares a highly conserved aa cluster with a non-PTS protein, the maize pyruvate:orthophosphate dikinase. The conserved cluster is located in a domain which is hypothesized to be the PEP-binding site.


Cloning and sequence analysis of the gene encoding an NADP-dependent alcohol dehydrogenase in Mycobacterium bovis BCG.

The nucleotide sequence of a 1619-bp fragment of Mycobacterium bovis BCG containing the gene that encodes an alcohol dehydrogenase (ADH) has been determined. The M(r) calculated from the deduced amino acid (aa) sequence, as well as the N terminus, are in good accordance with those determined for the ADH purified from M. bovis BCG extracts. The M. bovis BCG cloned adh gene was expressed in Escherichia coli by its own promoter and the synthesized product shows ADH activity in the butane-1-ol-NADP system. Based on comparison of the aa sequence, this enzyme belongs to the zinc-containing, long-chain alcohol/polyol dehydrogenase family, which has been primarily described in eukaryotes. Of the 22 strictly conserved residues in this group, 19 are also conserved in M. bovis BCG ADH (BCGADH).


The rate of decay of Rhodobacter capsulatus-specific puf mRNA segments is differentially affected by RNase E activity in Escherichia coli.

In Rhodobacter capsulatus the puf operon encodes proteins of the photosynthetic apparatus. The polycistronic puf mRNA is comprised of segments that show differential stability. Here, we show that the rate of decay of the 2.7-kb pufBALMX mRNA species in Escherichia coli depends on the activity of ribonuclease E (RNase E), whereas the degradation of the 0.5-kb pufBA mRNA segment is not affected by a mutation in the rne gene. The RNase E-promoted decay of the pufLMX mRNA depends on the presence of a 1.4-kb pufLM mRNA segment, in which rate-limiting endonucleolytic cleavage was postulated to occur in R. capsulatus. The insertion of 185 bp of this 1.4-kb segment into pufB results in an RNase E-dependent decay of the modified pufBA mRNA segment in E. coli. Our findings suggest that in R. capsulatus an RNase E-like activity is responsible for the rate-limiting endonucleolytic cleavage occurring within the pufLM mRNA segment, whereas the 0.5-kb pufBA mRNA segment is degraded by a different RNase E-independent decay mechanism.


Colonic and anorectal disorders: diagnosis and treatment.

Older patients are at increased risk of colonic and anorectal disorders, some of which occur commonly in patients of all ages. A careful medical history and physical examination, knowledge of the past medical history, and assessment of the circumstances in which symptoms of intestinal disease develop allows intelligent direction of the medical evaluation. Direct visualization of the colorectal mucosa using flexible fiberoptic or videoendoscopes often provides prompt and accurate diagnosis and facilitates therapeutic intervention. Other disorders require radiologic diagnosis and treatment or surgical intervention.


Health care for all: comparing proposals for reform. A roundtable discussion: Part 2.

Part 1 of this roundtable discussion [Geriatrics 1992; 47(Sept):34-48] examined the flaws in our current healthcare system and factors that are interfering with our nation's ability to achieve reforms. This month, the panelists discuss the benefits and drawbacks of the major healthcare reform proposals, including managed care, single-payer systems, and so-called "play or pay." The practical aspects of any redistribution of healthcare resources are considered as each panelist outlines a favored approach. The influence of special interests, such as the insurance industry, is also discussed.


A rational approach to urinary tract infections in older patients.

Urinary tract infections (UTIs) occur more commonly in the elderly than in younger adults. The frequency of concomitant chronic illness and decreased resistance in this age group confers increased rates of morbidity and mortality, and manifestations are often atypical. Diagnosis requires careful interpretation of urine culture results and a determination of the infection as asymptomatic bacteriuria, uncomplicated UTI, or complicated UTI. This, in turn, guides therapeutic measures, including the use of oral antibiotics.


Preventive nutrition: an 'optimal' diet for older adults.

Nutritional screening, an important aspect of prevention, includes measurement of height and weight, laboratory values as indicated, and a dietary assessment. For primary prevention, nutrition information should be broad enough to maintain health and prevent disease in healthy persons. Recommendations need to address problems of dietary excess as well as the possibility of nutrient inadequacy. Although controversial, the routine recommendation of a basic multivitamin and mineral supplement for healthy older adults is favored by these authors.


Preventive nutrition: disease-specific dietary interventions for older adults.

Disease prevention through dietary management is a cost-effective approach to promoting healthy aging. Fats, cholesterol, soluble fiber, and the trace elements copper and chromium affect the morbidity and mortality of CHD. Decreasing sodium and increasing potassium intake improves control of hypertension. Calcium and magnesium may also have a role in controlling hypertension. The antioxidant vitamins A and beta-carotene, vitamin C, vitamin E, and the trace mineral selenium may protect against types of cancer. A decrease in simple carbohydrates and an increase in soluble dietary fiber may normalize moderately elevated blood glucose levels. Deficiencies of zinc or iron diminish immune function. Adequate levels of calcium and vitamin D can help prevent senile osteoporosis in both older men and women.


Health care for all: long-term care, the missing piece. A roundtable discussion: Part 3.

Long-term care has been described as the "missing piece" in many healthcare reform proposals. Yet the cost of nursing home care often exceeds that of acute care, especially for the elderly with Alzheimer's disease. In this final installment of a three-part roundtable discussion, panelists discuss the options for providing long-term care, such as social insurance, a single-payer system, play or pay, or private insurance models. Alternatives to nursing home care, such as community service centers and home care, are discussed. The panelists conclude with an examination of how these proposed reforms might affect the practices of physicians and the U.S. economy.


Clinical evaluation of the patient with ventricular arrhythmia.

Evaluation of patients with ventricular arrhythmia (VA) is a frequently encountered problem in clinical practice. Determining which patients require treatment and which are at risk for sudden cardiac death remains challenging, however. Classification of VAs as significant, prognostically important, having unknown importance, or insignificant will help determine whether treatment is warranted and beneficial. Tests for evaluating suspected VA, including ambulatory electrocardiographic monitoring, exercise testing, and electrophysiologic studies, are used to determine the presence or frequency of an arrhythmia, correlate the arrhythmia with symptoms, determine a prognosis, or evaluate the efficacy of drug therapy.


Norepinephrine content in cardiovascular tissues from the aged Fischer 344 rat.

The major aim of the present study was to examine cardiovascular tissues and to determine if norepinephrine (NE) stores declined in aged (22-30 months old) male Fischer 344 (F344) rats. NE content was measured by HPLC in the whole heart, ventricle, atria, caudal artery, renal arteries, portal vein and kidney. The release of [3H]NE from the caudal artery of adult and aged rats was assessed as a functional index of sympathetic innervation. Renal alpha 2-adrenergic binding sites were also determined using 2.0 nM [3H]rauwolscine. In general, total NE content per organ was not altered in aged rats. The exception was the ventricle of aged rats which exhibited a 25% decrease in NE content. In contrast, NE content per gram of tissue weight was significantly decreased in the whole heart, atria, ventricle, kidney and caudal artery of aged rats when compared to that of adults (6-8 months old). Neither basal nor potassium-stimulated NE release was altered in the caudal artery of aged rats. Presynaptic regulation of NE release by taurine and alpha 2-adrenoceptors was also not affected by age. Renal alpha 2-adrenergic binding sites were decreased 23% in aged rats. Tissue growth that occurs as a function of aging does not appear to receive a concomitant increase in sympathetic growth as indexed by NE content. The findings of the present study would lead to the conclusion that with the exception of the ventricle, sympathetic nerve terminals of the aged male F344 rat are relatively intact.


Effect of propyl gallate feeding on glutathione content in ageing Zaprionus paravittiger (Diptera).

Glutathione content increased during the reproductive period and decreased thereafter up to the 43rd day of age in whole body as well as mitochondrial homogenates of ageing Zaprionus paravittiger. However, females exhibited higher levels of glutathione as compared to males. In whole body homogenates, propyl gallate (PG; 25 micrograms/ml) increased the glutathione content significantly up to the 22nd day of life whereas in mitochondria it increased during all age intervals in the two sexes with the exception of the 36th and 43rd day of survival in males. In conclusion, the higher level of glutathione on PG feeding might be one of the factors leading to the prolonged life span of flies.


Age-related changes in collagen of human intervertebral disks.

Age-related changes of human intervertebral disk collagen have been investigated. A progressive, age-related accumulation of collagen, both in annulus fibrosus and in nucleus pulposus was found. A decrease in collagen solubility was observed during physiological aging. Up to the 3rd-4th decades of life, a significant increase in the aldehyde content in disk collagen has been observed. Nuclei pulposi of the prolapsed disk contain more collagen, and its solubility was higher in comparison to corresponding necropsy material. Some alterations in the collagen of prolapsed disks may be considered as symptomatic of accelerated aging.


Hematocrit and cardiovascular risk factors among elderly men and women (Dutch Nutrition Surveillance System).

Changes in whole blood viscosity associated with hematocrit could be one of the pathways along which the cardiovascular disease (CVD) risk factors affect these diseases. Therefore, we studied in a nationwide survey comprising 514 apparently healthy Dutch elderly men and women aged 65-79 the possibility of any association between hematocrit and CVD risk factors (tobacco smoking, serum cholesterol, body mass index and blood pressure). Among men, diastolic blood pressure and total serum cholesterol were positively associated with hematocrit in both bivariate and multivariate regression analysis, whereas positive associations of hematocrit with body mass index and smoking were only significant (p < 0.05) in bivariate analysis. Among women, hematocrit was positively associated with body mass index and smoking. Except for smoking, which was associated with the mean corpuscular volume of the erythrocytes, hematocrit was positively correlated with hemoglobin and the number of erythrocytes. It is concluded that hemorrheological aspects should be considered when studying CVD among elderly people.


Nosocomial infection and antibiotic utilization in geriatric patients: a pilot prospective surveillance program in skilled nursing facilities.

Prospective surveillance of nosocomial infection was conducted at seven skilled proprietary nursing facilities in Orange County, Calif., USA. The average incidence of facility-acquired infection was 5.2 infections/1,000 patient days. The most common source of infection was urinary tract (47%), followed by respiratory tract (26%) and skin (14%). The four most common pathogens isolated were Proteus spp. (20%), Escherichia coli (17%), Staphylococcus aureus (13%) and Pseudomonas spp. (11%). Trimethoprim-sulfamethoxazole (20%) was the most frequently used antibiotic among all prescriptions, followed by ampicillin (16%) and ciprofloxacin (14%). Among all residents surveyed, 33% received at least one course of antibiotics during the study. Of special significance was the fact that 4 (22%) of the 18 strains of Pseudomonas were gentamicin resistant as were 12 of 80 (15%) of the strains of Enterobacteriaceae. Furthermore, 9 of 29 (31%) strains of Pseudomonas tested were found resistant to norfloxacin as were 15 of 129 (12%) strains of enterobacteriaceae. Susceptibility patterns of the isolated pathogens were similar to those of the acute care hospital. This study indicates that infection continues to be a major problem in the skilled nursing facility and that antibiotic-resistant pathogens will be a challenge for the future.


Leuko-araiosis and event-related potentials (P300) in normal aged subjects.

To investigate the relationship between cerebral leuko-araiosis and cognitive function in normal aged subjects, 48 neurologically normal aged volunteers (24 males, 24 females, 64-85 years old, mean age 75.2 years) with no silent lacunar lesions on their MRI images were examined. The severity of periventricular hyperintensity was estimated quantitatively based on the T1 values on MRI. Cognitive function was evaluated on the basis of P300 event-related potentials employing an auditory oddball paradigm. The severity of frontal lobe leuko-araiosis significantly increased with advancing age (p < 0.05), however, P300 latency was not correlated with age. There was no significant correlation between the severity of leuko-araiosis and P300 latency. The severity of leuko-araiosis was correlated with mean arterial blood pressure (p < 0.05). These results suggest that the severity of leuko-araiosis may be unrelated to cognitive function in normal aged subjects and that arterial blood pressure may contribute to the progression of leuko-araiosis.


Increased mechanical strength of left colon in old rats treated with growth hormone.

The effects of treatment with 2.7 mg biosynthetic human growth hormone (b-hGH; 2.7 mg/kg b.w./day) for 80 days on the biomechanical properties and collagen deposition of the left colon were studied in 27-month-old male rats. The b-hGH-treated rats increased in body weight by 17%, and the wet weight of colon by 31%. The defatted dry weight and the hydroxyproline content of the left colon were increased by 41 and 29%, respectively, compared with controls. The biomechanical analysis showed that the maximum load and stiffness of the left colonic specimens in the b-hGH-treated group were enhanced by 27 and 60%, respectively, and the strain at maximum load was 24% less than in the control group. The maximum 'stress' and stiffness were 40 and 73% higher, respectively, than in the controls. Histological examination demonstrated that the mean crypt heights was 9% higher in the b-hGH-treated rats than in the controls. Consequently, treatment of old rats with b-hGH may increase the strength, collagen deposition and mucosal crypt height of the left colon.


Changes in catalase activity and its thermolability in liver and kidneys of ageing male garden lizard.

Catalase activity in liver and kidneys of male garden lizards remained unchanged during maturation, but showed an increase during ageing. Instead of inactivating catalase, thermal treatment at 60 +/- 1 degree C caused a marginal increase in enzyme activity in the liver of middle-aged and kidneys of young lizards with no significant effect in old counterparts. Increase in basal enzyme activity during ageing and the maintenance of resistance against thermal inactivation of the enzyme throughout the life-span support the contention that catalase molecules in lizard tissues are not altered as a function of age, a deviation from the predictions of Orgel's error catastrophe hypothesis.


Participation of decreased serum cholesteryl ester transfer activity, independent of increased serum lipoprotein(a), in angina pectoris in normolipemic elderly subjects.

The cholesteryl ester transfer activity (CETA) is a measurement of the transfer of cholesteryl ester from HDL to VLDL, LDL or peripheral cells. Its role in the development of early coronary heart disease is not clear. In the present study, serum levels of CETA, lipoprotein(a) [Lp(a)] and other lipid-related factors were compared in 10 normal young subjects, 28 healthy elderly subjects and 14 normolipemic elderly patients with angina pectoris. Compared to the young normals and healthy elderly subjects, the elderly patients with angina pectoris showed significantly decreased mean serum CETA levels, and significantly increased mean serum levels of Lp(a) and apoprotein B. These results may indicate that decreased serum values of CETA participate in the development of angina pectoris in normolipemic elderly patients.


An investigation of the relationship between free radical activity and vitamin C metabolism in elderly diabetic subjects with retinopathy.

Abnormalities of both free radical activity and ascorbic acid metabolism have been documented in diabetes, but their biological basis is unclear and their relationship unstudied in any detail. This study was designed to compare changes in antioxidant status and free radical reactions in a group of elderly diabetic patients (with and without retinopathy) with those in a group of age-matched control subjects. No significant differences in thiobarbituric acid (TBA) reactivity, red cell glutathione (GSH) concentrations or diene conjugates (DC) between patients and controls were seen despite significant depletion of ascorbic acid in patients with diabetes, especially in those with retinopathy. The results emphasise the present-day difficulties of measuring free radical activity and demonstrate a marked abnormality in ascorbic acid metabolism in diabetes.


Lack of association of nonsteroidal anti-inflammatory drug use and cognitive decline in the elderly.

Folstein Mini-Mental State Examination (MMSE) scores obtained in an ambulatory elderly population were used to examine the effect of nonsteroidal anti-inflammatory drug (NSAID) use on cognitive performance. There were 1,310 participants who met the inclusion criteria for the study, of whom 873 (66.6%) were women and 437 (33.3%) were men. There were no differences in mean MMSE scores or in the five dimensions of cognitive function measured by the MMSE for subjects reporting NSAIDs or aspirin use.


Vitamin-D-fortified liquid milk--a highly effective method of vitamin D administration for house-bound and institutionalised elderly.

The aim of the study was to assess the efficacy and acceptability of vitamin-D-fortified liquid milk in the management of hypovitaminosis D in an elderly institutionalised population. The design was a single-blind randomised controlled study. In phase I, patients were encouraged to drink an increased quantity of either fortified or unsupplemented milk for 3 months. In phase II, patients were continued on either fortified or on unsupplemented milk which was given as part of the everyday diet for a further 6 months with no extra encouragement of any patient to take additional amounts. Ninety-eight patients (mean age 84 years) from extended care wards at the Department of Medicine for the Elderly, St. James's Hospital, Dublin, Ireland, participated in the study. Seventy-eight patients completed phase I, and 62 completed phase II. A general biochemical screen and 25-hydroxy vitamin D measurements were performed at entry and repeated 3 and 9 months later. The average milk intake per patient in phase I was 454 ml/day in the unsupplemented group and 359 ml/day in the fortified milk group. In phase II, the average daily milk intake per patient was 235 ml in the unsupplemented milk group and 140 ml in the fortified milk group. Seventy-four patients (94%) of the total who completed phase I had serum vitamin D baseline levels below the normal range. In the fortified milk group, mean vitamin D levels rose from 2.4 to 14.80 ng/ml (p < 0.001) at the end of phase I and remained significantly elevated at 10.2 ng/ml (p < 0.001) at the end of phase II.(ABSTRACT TRUNCATED AT 250 WORDS)


Brain atrophy on computerized axial tomography scans: interaction of age, diabetes and general morbidity.

We evaluated, retrospectively, the occurrence of brain atrophy in all patients (n = 416) with a brain CT scan performed during a 3-month period in 1989 at the Tampere University Central Hospital. Age, diabetes, hypertension, chronic cerebrovascular disorders and an increasing number of medications were associated with brain atrophy in the log-linear models. We suggest that the effect of various systemic medical disorders on the brain requires consideration when evaluating and assessing physiological ageing of the brain.


Randomised controlled trial of exercise in the elderly.

Eighty-seven healthy volunteers aged 60-81 years were randomly allocated to either an aerobic exercise class or a health education group. Only 6 subjects dropped out during the 32-week study, and the average compliance with the interventions was 83% for exercise (on average 83/100 individual exercise sessions were attended) and 71% for health education. The health education group showed improvements from the baseline in physical activity levels, pulse rate, blood pressure and self-rating of mood. The exercise group improved from baseline in knee and spine flexibility, leg and back strength, pulse rate, blood pressure, maximum physical exertion levels, self-rating of mood and perceived health status. Between group comparison at the end of the study showed the exercise group significantly better than the health education group in terms of spine flexion (p < 0.0001), perceived health status (p < 0.05), life satisfaction (p = 0.05) and maximal physical exertion (p = 0.01). This study has demonstrated the acceptability and effectiveness of an aerobic exercise class for the elderly, and the effectiveness of health education for this age group.


Exfoliation syndrome as a risk factor for optic disc changes in nonglaucomatous eyes.

Exfoliation syndrome as a possible risk factor for morphologic changes of the optic nerve was examined in 66 patients with unilateral exfoliation and no glaucoma. K-readings (7.74 +/- 0.3 mm and 7.75 +/- 0.3 mm), axial lengths (23.1 +/- 1.1 mm and 23.1 +/- 1.1 mm), and refraction (+ 0.9 +/- 2.3 mm and + 1.1 +/- 2.3 mm) did not differ in exfoliative and contralateral nonexfoliative eyes. The mean intraocular pressure (IOP) difference, 17.2 +/- 3.3 mmHg and 15.6 +/- 3.2 mmHg, respectively, was statistically highly significant (P < 0.001). The mean visual acuity difference, 0.8 +/- 0.3 and 0.9 +/- 0.2, respectively, was significant (P < 0.05). The difference in visual acuity between the pairs of eyes was explained by the more frequent subcapsular cataract in exfoliative eyes. Lens opacity values (opacity lens meter), 27.9 +/- 8.3 and 28.0 +/- 8.4 opacity units, respectively, were similar. Disc area, neuroretinal rim area, rim/disc ratio, cup area, and cup volume values analyzed with the Imagenet (Topcon) nerve head analyzer did not differ significantly between the eyes. It was concluded that exfoliation as such does not induce optic nerve head changes but indicates a risk factor for elevated IOP and lens opacification.


Count and density of human retinal photoreceptors.

This investigation was directed at determining the count and regional distribution of photoreceptors in the eyes of 21 human cornea donors aged between 2 and 90 years. Mean count of rods was 60,123,000 +/- 12,907,000, and mean cone count was 3,173,000 +/- 555,000. Determined 40 microns away from the foveola, cone density measured 125,500 cones/mm2. Extrapolating the distribution curve, cone concentration in the foveal center can be assumed to be about 150,000 cells/mm2 to 180,000 cones/mm2. Towards the retinal periphery, cone density decreased from 6000 cones/mm2 at a distance of 1.5 mm from the fovea to 2500 cells/mm2 close to the ora serrata. Comparing different fundus regions, cone concentration was significantly highest in the nasal region. Cone diameter increased from the center towards the periphery. At a distance of 40 microns away from the foveola, it measured about 3.3 microns, and in the outer retinal regions about 10 microns. Rod density was highest in a ring-like area at a distance of about 3-5 mm from the foveola with a mean of 72,246 +/- 17,295 cells/mm2. Rod density peaked at 150,000 rods/mm2. It decreased towards the retinal periphery to 30,000-40,000 rods/mm2. Rod diameter increased from 3 microns at the area with the highest rod density to 5.5 microns in the periphery. The hexagonal rod and cone inner segments were regularly arranged in a honey-comb fashion.


Parameters associated with papillomacular bundle defects in glaucoma.

To evaluate the relationship between the papillomacular bundle defect and glaucoma types, abnormalities of the optic disc, distance between the disc and foveola, and axial length, we examined one eye of 82 patients with normal tension glaucoma, 117 patients with chronic high tension glaucoma, and 102 controls. Two types (diffuse and focal types) were found in the papillomacular bundle defect, and the former predominated. Eyes with a long axial length (P < 0.01), a diagnosis of normal tension glaucoma (P < 0.05), or a large optic disc (P < 0.05) tended to have diffuse-type papillomacular bundle defects, while eyes with a short axial length, a diagnosis of high tension glaucoma, or a large ovalness index are less likely to have it. Thus, a long axial length, a large optic disc, and normal tension glaucoma are risk factors for the diffuse-type papillomacular bundle defect.


Acetazolamide but not timolol lowers aqueous humor flow in sleeping humans.

The effect of timolol, acetazolamide, and the combination of the two drugs on the rate of aqueous formation in 18 healthy human subjects was measured during the day and at night in a placebo-controlled, double-masked, randomized study. In the absence of any drugs, aqueous flow during the day was 2.61 +/- 0.82 (mean +/- SD) microliters/min and at night, 1.08 +/- 0.59, a 59% lower flow rate when compared with the daytime value (P < 0.0001). When compared with these aforementioned control values, timolol alone reduced the rate of aqueous flow by 39% (P < 0.0001) in awake subjects but had no statistically significant effect on the flow rate in sleeping subjects (P = 0.33). Acetazolamide alone reduced aqueous flow during the day by 21% compared with the control flow rate (P = 0.02) and at night by 24% below the nocturnal flow rate in the sleeping eye (P = 0.04). The combination of the two drugs reduced flow during the day by an additional 13% (P = 0.024) compared with the flow rate achieved by timolol alone, and by an additional 32% (P < 0.0001) compared with the flow rate reduction attained by acetazolamide alone. There was no statistically significant difference in the nocturnal flow rates achieved by acetazolamide alone or in combination with timolol (P = 0.37). These data confirm previous studies demonstrating the effect of timolol, acetazolamide, and sleep on the rate of aqueous humor formation. Unlike a previous study, it was found that acetazolamide lowers the aqueous flow below the already low nocturnal flow rate that occurs spontaneously in the sleeping eye.(ABSTRACT TRUNCATED AT 250 WORDS)


The relationship between intraocular pressure and visual field progression in glaucoma.

The purpose of this study was to determine the intraocular pressure characteristics in glaucoma suspects and patients whose visual fields were classified as stable or progressing over a long-term follow-up. We present data from 64 patients who received either medical or laser treatment and who were followed up for a median of 7.4 years. The visual fields of 27 patients were classified as stable and 37 as progressing using predetermined criteria on either the Tübinger or Goldmann perimeter. Patients with initially normal and initially abnormal fields were analysed separately to avoid bias. There were no significant group differences in the mean, highest or interquartile range of intraocular pressure in the follow-up. The largely overlapping distributions over a wide spectrum of the pressure variables in patients with stable and progressing fields show that intraocular pressure alone cannot separate these two groups of patients. Our study does not suggest that pressure reduction in glaucoma has no beneficial effect, but that there may be other factors which determine the fate of the visual field in glaucoma.


Metastatic tumors to the orbit--management and prognosis.

In a retrospective study the records of 34 consecutive cases with tumors metastatic to the orbit were reviewed with special attention to the management and prognosis of these patients. The primary tumor site was the breast in 20 patients, prostate in 5, kidney in 2 and skin in 2. The remaining 5 patients had other primary tumour sites. The symptoms of orbital metastasis preceded the detection of the primary tumor in 8 cases (24%). Twenty patients died after a mean interval of 25 months following the diagnosis of the orbital metastasis. This study gives a summary of the clinical features of these patients. With improved methods of treatment it was possible to obtain a relief of orbital symptoms in 24 patients (71%). Although the life expectancy of these patients remains poor, treatment can result in symptomatic relief and in an improvement in the quality of life, which is the main goal in the management of these patients.


The pathology of abortive neovascular outgrowths from the retina.

Seven abortive neovascular outgrowths (ANVOs) from diabetic retinas were obtained for examination either by biopsy during pars plana vitrectomy (2) or after discovery within enucleated globes (5). Scanning and electron microscopical, histochemical, immunohistochemical and retinal digest techniques were used. The ANVOs consisted of nodules of vessels without an extravascular fibrous component. Two of them contained aneurysm-like dilatations of constituent vessels, and all the specimens showed gross hyaline thickening of the vessel walls. The vascular sclerosis was probably due to accumulation of plasma proteins in the walls of the damaged vessels, which contributes to their involution seen clinically after retinal photocoagulation.


Use of the argon laser to close filtering bleb leaks.

We attempted to seal 15 consecutive filtering bleb leaks in 11 patients using argon laser energy. Eight leaks were at the conjunctival-corneal interface associated with a fornix-based flap, 4 leaks resulted from suture scissoring of the conjunctiva, and 3 leaks were button-holes in the conjunctiva. Thirteen leaks occurred within 2 weeks after filtering surgery, while 2 were of late onset. Argon laser parameters used were a 500-microns spot size, 0.1-s time interval, and between 500 and 1800 mW of power. Thirteen leaks were sealed after one or two laser sessions, while 2 leaks required other treatment modalities. Complications included conjunctival fenestration and transient corneal stromal opacities. This study suggests that the argon laser can be used to seal filtering bleb leaks in many patients following filtering surgery.


Intraocular pressure-related pattern of optic disc cupping in adult glaucoma patients.

The pattern of glaucomatous optic disc cupping was investigated in 67 eyes of 67 primary open-angle glaucoma patients with early-to-moderate visual field loss and a wide range of intraocular pressure. We determined the position of the deepest point of the optic disc cup using the Rodenstock Analyzer. This position correlated significantly with intraocular pressure: the deepest point tended to be located below the center of the optic disc at high intraocular pressure and above the center at low intraocular pressure. There was no significant correlation between the position of the deepest cup point along the horizontal axis and intraocular pressure. The position of the deepest point of the cup also correlated significantly with the severity of glaucoma, albeit less strongly than with intraocular pressure: it tended to be in the inferior portion of the disc at an early stage of glaucoma and in the superior portion of the disc at a more advanced stage of glaucoma. Therefore, the inferior portion of the optic nerve head appears to be most yielding to changes of intraocular pressure. These findings are consistent with histologic evidence of the least connective tissue support in the inferoperipheral region of the lamina cribrosa and with greater prevalence of inferior rim loss and corresponding superior visual field defects in early to moderately advanced primary open-angle glaucoma patients.


A laboratory evaluation of the Kowa laser flare-cell meter for the study of uveitis.

The Kowa FC-1000 laser flare-cell meter (LFCM) has been described as an instrument which will objectively quantify inflammation of the anterior chamber of the eye. We evaluated the LFCM using the intravenous endotoxin-induced uveitis (EIU) rabbit model of ocular inflammation. In vitro flare and cell calibration measurements utilizing bovine serum albumin (BSA) and latex particles, respectively, were also performed. A linear relationship between the flare measurements and BSA concentrations was noted. In addition, the time course of the LFCM flare count in EIU was comparable to previously published fluorophotometric data. However, the LFCM reported cells in the anterior chamber of the EIU rabbits despite negative cytology and histology results. The LFCM also recorded cells in BSA solutions which contained neither cells nor latex particles. Our results suggest that although the LFCM may be useful for evaluating flare, its cell measurements are not accurate in cases of severe uveitis.


Are large optic nerve heads susceptible to glaucomatous damage at normal intraocular pressure? A three-dimensional study by laser scanning tomography.

To evaluate the effects of the presence of glaucomatous visual field defects and of intraocular pressure elevations on optic nerve head topography, we analyzed 148 left optic nerve heads of 148 patients using laser scanning tomography. The optic discs are classified according to computerized static perimetry and documented IOP readings: 101 discs show normal visual fields (36 normal discs, 22 ocular hypertensives, 28 normotensive glaucoma suspects and 15 ocular hypertensive glaucoma suspects), 47 discs (34 high-pressure glaucoma discs, 13 normal-tension glaucoma discs) demonstrate glaucomatous visual field damage. A two-way analysis of variance discloses significant differences (P < 0.01) between the groups of optic discs classified according to perimetry for most topometric parameters evaluated except for disc area. Classification according to documented IOP (cut off at 21 mmHg) results in larger disc areas in normotensive discs compared to hypertensive optic nerve heads in the study population. Results suggest that large discs may be susceptible to glaucomatous visual field damage at statistically normal IOP readings.


Dysfunction of the blood-retina barrier following white light exposure. A tracer study with horseradish peroxidase and ferrous gluconate.

The aim of this investigation was to study the ultrastructural effects of white light on the retinas of pigmented rabbits. The retinas were exposed to white light (400-740 nm) at intensities between 65 and 140 mW/cm2 for 1 h. Two days after exposure, the increased leakage of fluorescein measured with vitreous fluorophotometry could be mimicked on electron microscopy by the tracers ferrous gluconate and horseradish peroxidase (HRP). In cases of minimal fluorescein leakage, traces of HRP were found in the basal folds of the retina pigment epithelium (RPE). No HRP was observed apical to the tight junctions of the RPE cells. When there was a great amount of fluorescein leakage, HRP completely filled the RPE cytoplasm, the extracellular spaces, and several cells in the neuroretina. It is concluded that after exposure to low intensities of white light, blood-retina barrier dysfunction may be due to disruption of the RPE basal fold membrane, leading to increased transcellular passage. The intact tight junctions suggest the under these circumstances intercellular leakage is not a component of BRB dysfunction.


Late ultrastructural changes in the retina of the rat following low-dose X-irradiation.

This study describes ultrastructural changes in the pigmented hooded Lister rat retina, 3-12 months following X-irradiation with single doses of between 200 and 2000 cGy. The extreme radiosensitivity of the photoreceptor cells was underlined by the continued manifestation of fine structural changes and cell death up to 6 months post-radiation in animals receiving doses above 500 cGy. The retinal pigment epithelial (RPE) cells were more radioresistant than photoreceptors and RPE cell loss was only observed at doses of more than 1500 cGy. One year after irradiation with 1500 cGy the retinal vasculature showed capillary occlusion with some evidence of recanalisation. Telangiectasia was observed in the large retinal veins. Although the inner retinal neurones and glial cells showed no evidence of direct radiation damage, the nerve fibre layer adjacent to occluded retinal vessels demonstrated ultrastructural evidence of ischaemic neuropathy and retinal oedema. At doses above 1500 cGy the choriocapillaris showed platelet aggregation and capillary loss.


Nerve terminal degeneration in the rat iris observed following chronic topical 2% epinephrine and 0.1% dipivalyl epinephrine: a quantitative comparison of electron microscopic observations and tissue norepinephrine levels.

This is the first report of nerve terminal degeneration within the iris following topical dipivalyl epinephrine 0.1% treatment. A quantitative comparison of the effects of topically applied epinephrine 2%, dipivalyl epinephrine 0.1%, and placebo vehicle on the nerve terminals within the iris of a rat was made using electron microscopy and a catecholamine radioenzyme assay. Thirty-nine rats were divided into these 3 treatment groups and treated for 10 weeks, after which they were killed and studied. Both the epinephrine 2%- and dipivalyl epinephrine 0.1%-treated groups showed greater nerve terminal degeneration compared with the placebo-treated group (P < 0.05). The epinephrine-treated group showed greater nerve terminal degeneration than the dipivalyl epinephrine-treated group. The clinical significance of these observations is unknown. It is impossible to decide whether these degenerative changes are related unavoidably to a desired therapeutic effect or to an undesirable, potentially avoidable, toxic side effect.


Light and lithium effects in the rat retina: modification by the PAF antagonist BN 52021.

We tested the effect of an antagonist of platelet-activating factor (PAF), BN 52021, on both acute light-induced and light plus lithium-induced rod outer segment (ROS) lesions. Rats were fed lithium carbonate (2.6 g/kg chow) for 3 weeks. Half of the lithium-treated rats received BN 52021 (25 mg/kg) via gastric intubation prior to light exposure. Control and treated rats were exposed to 400-450 lux (measured at the eye level of the rats) of diffuse, white fluorescent light for 30 min, followed by 2 h of darkness and then decapitated. The eyes were removed and prepared for light and electron microscopic observation. The structural alterations of ROS were quantified from electron micrographs using a multifunctional computer image-analysis system. Our data show a significant reduction of ROS lesions by BN 52021, and this is most pronounced in light plus lithium-treated rats. Furthermore, in confirmation of previous studies, chronic lithium treatment significantly augmented light-elicited phagosome numbers, and BN 52021 reduced this effect. Our findings thus suggest that light and lithium may act via PAF responses in the rat retina.


The effect of sodium iodate on the blood-retinal and blood-brain barriers.

Both active transport through and permeability of the blood-retinal barrier (BRB) are affected by sodium iodate, while the blood-brain barrier (BBB) is more resistant. We studied the effect of sodium iodate on facilitated diffusion through the two barriers. The retinal (RUI) and brain (BUI) uptake indices were determined for D-glucose and two neutral amino acids in normal and sodium iodate-treated rats. The integrity of the barriers was estimated by RUI and BUI for L-glucose and by measuring tissue uptake of L-glucose after an intravenous injection. We found that 30 mg/kg sodium iodate had no effect on transport through or permeability of the BBB, while 20 mg/kg significantly (P < 0.02) reduced transport of D-glucose, but not amino acids, through the BRB 1 h after injection. After 24 h both 20 mg/kg and 30 mg/kg sodium iodate caused a significant disruption of the BRB (P < 0.005 and P < 0.001, respectively). Thus, sodium iodate selectively affects the carrier for D-glucose in the BRB but not in the BBB. The presence of an epithelial part in the BRB, the retinal pigment epithelium, may explain the difference between the two barriers.


Systemic candidiasis in babies with retinopathy of prematurity.

Fifteen premature babies developed systemic candidiasis during the administration of intravenous hyperalimentation in the Beilinson Neonatal Intensive Care Unit. Candida albicans was found in the blood cultures of all the babies and in the urine cultures of 66.7% of them. Repeated funduscopic examinations revealed no evidence of septic embolization in the retinal or choroidal circulation. It should be noted that acute retinopathy of prematurity (ROP) grade 2 or 3 was found in all the babies.


Is there an association between optic disc drusen and angioid streaks?

We reviewed the color photographs and fluorescein angiograms of 110 subjects with angioid streaks. Evidence is presented for an association between drusen of the optic disc and angioid streaks.


[The indicator system of the fetoplacental complex for evaluation of the condition of atmospheric air].

Interrelationship between the structure-and-function changes in feto-placental complex and the worsening health status and development of children in arms effected by the chemical pollution of the ambient air was shown. Feto-placental changes expressed in decreasing of the protein and nucleic acid content and increasing of membrane permeability.


[Toxicological characteristics of sebacic acid and the substantiation of its maximum permissible exposure level in atmospheric air].

Average daily MAC of the sebacic acid in the ambient air established at the level of 0.05 mg/m3 (3-d class of hazard). Data of acute and chronic experiments were noted.


[Current status and tasks of sanitary-protozoological studies of drinking water (review of the literature)].

Occurrences of giardiasis in the USA, Canada, Great Britain and other countries caused by drinking water were noted. Necessity of sanitary-and-protozoological inspection of the drinking water in the USSR was demonstrated.


[Hygienic substantiation of standardization of the iron level in hot water of the central heating system in residential areas].

Epicutaneous applications of the iron trivalence caused the sensibilization of mice. The effect depended on the temperature.


[Hygienic evaluation of working conditions in present-day production of welding electrodes].

Complex of unhealthy factors in the welding electrodes production was estimated. The leading ones are the high level of the noise and high concentration of the manganese dioxide aerosol in air. Toxicochemistry of the action of these factors was discussed.


[Use of the "exposure level-body condition" relations for evaluation of the effects of complex atmospheric pollution].

Criteria for the organism status arrangement in terms of environmental effects expression from adaptation to its break-down were worked up. The criteria may be used in developing of the hygienic standardization of environmental effects.


[A rapid method of evaluation of the effects of environmental factors on the degree of stress in human regulatory mechanisms].

A basically new approach and a "Diagnoz" apparatus based on the one-stage recording of information processing rate and skin electric resistance were developed. The nervous system stress may be evaluated by the method in hygienic studies.


[Allergic effects on the population of industrial air pollutants].

Increasing of the allergization of the population in industrial regions caused by chemical pollution of the air was noted. Some changes in respiratory tract and blood count were reported also.


[A hygienic evaluation of the new flocculant polyhexamethyleneguanidine].

Sanitary and toxicological study of some guanidine containing polymers was done. Moderate toxicity of the polymers and absence of any specific effects were noted.


[An experimental validation of the MPEL for the Zharilek mixture and its component constituents].

"Zharilek" preparation MAC in the water reservoirs was approved at the level of 0.01 mg/l. The preparation is referred to the 3rd class of hazard by the complex toxicological study.


[The late effects of exposure to lead fluoride].

Effect of lead fluoride dust on the micronuclear reticulocyte content in the bone marrow was shown. Some functional changes in the testicles and increase in the fetal death rate in exposure to 50 mg/m3 of lead fluoride dust were noted.


[The nutritional prevention of postradiation effects].

Radioprotective effects of vitamin complexes were shown. Author issued the possible mechanisms of the phenomena.


Impact of self-management education on the functional health status of older adults with heart disease.

This paper presents findings from the evaluation of a self-management education program based on self-regulation principles. Older men and women (N = 324) were randomly assigned to program and control groups. Outcomes were measured using the Sickness Impact Profile. Twelve months following baseline data collection, psychosocial functioning of program participants was significantly better than that of controls. Different program effects were noted when results were analyzed by participant gender.


Exercise beliefs and behaviors among older employees: a health promotion trial.

This health promotion trial included university faculty and staff aged 50 to 69 who had completed a health risk screening. Predictors of intention to exercise were education, gender, self-efficacy, outcome expectancy, perceived barriers, and baseline exercise frequency. Baseline exercise frequency was the only predictor of exercise behavior 1 year later.


Attempts to prevent falls and injury: a prospective community study.

At 16 senior centers, we studied the effectiveness of exercise and cognitive-behavioral programs, compared with a discussion control program, in reducing falls and injuries among 230 older adults. After 1 year of the programs, we observed no significant difference in time to first fall. Even though a relatively high percentage (38.6%) suffered at least one fall, only 7.8% of these community-residing elderly required medical attention. Secondary outcome measures such as strength, balance, fear of falling, and perceived health did not significantly change.


Housing emergencies and the etiology of homelessness among the urban elderly.

This research examined factors that lead to homelessness and shelter placement of seniors. A purposive sample of 475 aged clients was selected randomly from the files of a citywide emergency service program, 45% of whom were found to have had serious housing-related problems. A subsample of 115 housing problem cases was investigated, including persons who had needed emergency shelter or temporary housing or been living in deteriorated housing. Assessment data from the OARS instrument and open-ended housing history questions were analyzed. Homelessness was found to be significantly associated with low income, dementia, living alone, and an unstable residential history.


Project rescue: serving the homeless and marginally housed elderly.

The authors describe the engagement techniques and service components of a program for homeless and marginally housed elderly. On follow-up evaluation of 132 people, clients averaged three favorable outcomes (maximum = 7). Service delivery was conceptualized as a three-stage process based on the differential effects that variables had at each stage. The strongest predictors of outcome were number of service encounters, type of presenting problem, and perceived level of social support.


Did tax reform hurt the elderly?

Federal and state income tax reform increased aggregate federal tax payments of elderly taxpayers by just over 5% and their aggregate state taxes by about 6%. However, the entire increase is accounted for by the elderly in the top income decile. The mean change in total income taxes paid by the elderly was $135, but the median increase was zero because most older persons paid no federal or state income tax before or after tax reform. The overall effect of tax reform was a slight shift in income tax burdens from the nonelderly to the elderly reversing a trend dating from the late 1970s.


Economic rationality, the affordability of private long-term care insurance, and the role for public policy.

This study uses data from the 1984 panel of the Survey of Income and Program Participation (SIPP) of the U.S. Bureau of the Census to develop new estimates of the potential market for private long-term care insurance. It found that this market is potentially significant--especially among individuals in the 65-69 age group who are willing to spend up to 50% of their discretionary income on such insurance--but considerably lower than previous estimates, such as those of Cohen and colleagues (1987).


Difficulties and rewards in family care of the depressed older adult.

Spouse and adult child caregivers of older adults with major depressive disorder (N = 150) were asked what was most difficult and most rewarding about providing assistance to their relatives. Content analysis of their responses revealed seven areas of difficulty and three areas of reward. Difficulties and rewards were selectively associated with the caregiver's identity, patient clinical characteristics, and caregiver emotional adjustment. Caregiver perceived family difficulties and emotional difficulties were associated with the course of patient psychiatric illness over 1 year.


Severe family violence and Alzheimer's disease: prevalence and risk factors.

This study describes the prevalence of violence and the putative risk factors for violence in 184 Alzheimer patients and their primary caregivers living in the community. Analysis of the severe violence subscale of the Conflict Tactics Scale indicated that 15.8% of patients had been violent in the year since diagnosis. A total of 5.4% of caregivers reported being violent toward the patient. The overall prevalence of violence was 17.4%. The variables most associated with violence were caregiver depression and living arrangement.


Gender differences in caregiving: fact or artifact?

This study applies meta-analysis techniques to the results of 14 descriptive studies of gender differences in caregiving to determine the size and significance of gender differences in caregiving stressors (level of elder impairment and level and type of task involvement) and in caregiver burden. There were essentially no significant gender differences in functional impairment of the frail care recipient, total caregiver involvement in care, or in money management tasks. Female caregivers were more likely to carry out personal care and household tasks and more likely to report greater burden. Given the relatively small size of the effects found, we conclude that future research should focus on the part that gender-role explanations play in assigning meaning to caregiving behaviors.


Adjustment among different age and ethnic groups of Indochinese in the United States.

This study examines adjustment among different age and ethnic groups of Indochinese refugees in the United States. The data came from a nationwide probability sample of 3,414 respondents aged 20 or older. Respondents are divided into four age groups (20-29, 30-39, 40-54, and 55 and older). Ordinary least squares regression analysis revealed that education, occupational status, urban/rural location in the country of origin, English language ability, financial problems, gender, age, and length of residence in the U.S. had statistically significant relationships with adjustment in different age and ethnic groups.


Parental dependence and filial responsibility in the nineteenth century: Hial Hawley and Emily Hawley Gillespie, 1884-1885.

This paper examines diaries written by an Iowa farm woman and her daughter in the 1880s that focus on care of the former's father. It highlights the problems intergenerational living arrangements could produce in the 19th century. In addition, it examines three general themes: the impact on adult children of financial responsibility for elderly parents, the responses of elderly people to structures of subordination, and the significance of hierarchies of gender as well as generation.


Alternative sources of social support and their impacts on institutional risk.

We examined the direct and buffering effects of different dimensions of social support on the risk of being institutionalized over a 2-year period. Multivariate analyses indicated that specific aspects of social support, such as having a spouse or adult child caregiver, or having a caregiving relationship of at least 3 years' duration, moderated the impact of one type of stress (being highly dependent on others for care) on the risk of entering a nursing home. Networks that included a paid provider modestly offset the impact that multiple IADL impairments had on being admitted at least once to a nursing home.


Blood pressure measurements in the nursing home: are they accurate?

To examine the accuracy of blood pressure (BP) measurements in the nursing home, a trained observer (physician) and nursing home staff (NHS) measured BP for 146 nursing home residents on two separate occasions. Using the physician as the reference standard for measuring BP, the NHS: 1) significantly underestimated systolic BP; 2) significantly overestimated diastolic BP; and 3) had a high frequency of terminal digit preference for zero. These errors resulted in the NHS misclassifying hypertension in 21% of patients.


Impact on caregivers of supporting urinary function in noninstitutionalized, chronically ill seniors.

In a multivariate study of 148 caregivers of chronically ill older persons, 22% of those caring for a continent senior reported that maintaining continence was a burden, and 75% of caregivers of incontinent seniors reported it as burdensome. The burden of maintaining urinary function was associated with lack of social support, time spent providing care, and care receiver's immobility. Caregivers' depressive symptoms were associated with perceived burden from providing care for urinary function, a confused care receiver, and post-stroke support.


Physicians' acceptance of behavioral treatments and pharmacotherapy for behavioral disturbances in older adults.

In response to growing interest in employing behavioral treatments and environmental modification for behavioral disturbances in older adults, we employed vignette methodology to examine physicians' acceptance of two behavioral treatments and haloperidol using Kazdin's Treatment Evaluation Inventory. Physicians assigned the highest acceptability ratings to the behavioral treatments and the lowest ratings to haloperidol. The patient's cognitive capacity, living situation (nursing home vs. community), and the type of behavior problem mediated treatment acceptability ratings.


Enhancing the self-esteem of selected male nursing home residents.

This study investigated treatment procedures for enhancing the self-esteem of older adult male nursing home residents. Twenty-one subjects were assigned randomly to either a control group meeting to discuss current news events or an experimental group receiving the intervention. Self-esteem significantly increased for the experimental subjects but not before they experienced a significant decrease in feelings of self-worth. The midtreatment observation of the dependent variable was a vital factor in determining the curvilinear relationship between time and the protocol.


Transportation as outreach, driver as mental health worker.

Case finding and early detection and referral of elderly persons with mental problems can be accomplished by trained and supervised drivers as part of a transportation service. Increased access to community programs and services as a result of provided transportation helped clients maintain their independence and self-esteem.


Voting behavior among low-income black elderly: a multielection perspective.

We examined voting behavior among 370 low-income older African-American citizens who reside in New Orleans by assessing the impact of various predictors on electoral participation in a series of seven elections. Elders who were active in their community, with a strong sense of citizen duty, who identified themselves as strong Democrats, and with higher levels of education were more likely to vote.


The political behavior of older American blacks.

Using a subsample of the National Opinion Research Center's 1987 General Social Survey, this study examined three competing explanations for the political behavior of older black Americans (n = 157, 55 and older). The socioeconomic model was a good predictor of political behavior; ethnic community theory and the empowerment model were, in varying degrees, predictors of alienation but not of political interest or activity. Some comparisons were made between older black Americans, younger blacks, and older and younger whites.


Older voters and the 1992 presidential election.

At the core of the so-called "generational equity" construct is the notion that older persons exercise self-interested political power. This article examines what we know about one element of the politics of aging--the voting behavior of older persons in recent presidential elections--and suggests areas of research on the 1992 election that may tell us something about how far, and how soon, proponents of generational equity will be able to move toward dismantling policies that benefit older people.


Women as family caregivers: why do they care?

This study was based on in-depth qualitative interviews with 40 francophone Québécois family caregivers of frail elderly or mentally ill relatives and focused on the caregiving relation rather than on the specificities of aging and mental illness. Fourteen factors (love, guilt and duty, women's social identity built around caring, absence of appropriate public or private care alternatives, women's socioeconomic dependence, etc.) emerged from an analysis of informants' accounts of how they came to be the primary caregiver. Data indicate that analyses attempting to understand women's caregiving must take into account the sexual division of labor, its reinforcement through social policy, and how women internalize ideas and norms regarding appropriate gender-role behavior.


A path not taken: a cultural analysis of regrets and childlessness in the lives of older women.

This paper explores regrets about childlessness in 90 older women interviewed using qualitative methods. Regrets were discussed in the context of the changing meaning of childlessness over the life course. We found that issues of regret are situated in a cultural system that renders childless women marginal. We argue that regrets should be understood in a wider cultural context that incorporates the cultural construction of the self over time.


The role of animal models in meeting the gerontologic challenge of the 21st century.

Animal models play an important role in our quest to understand aging and develop interventions needed for the gerontologic challenge of the 21st century. Results from studies using the dietary restriction rodent model are presented as an example. Dietary restriction slows aging by inhibiting primary aging processes, by enhancing broadly protective mechanisms, or by both. Further study should identify the mechanisms and yield a data base for development of interventions. A threat to attaining these yields is the growing opposition of some to this use of animals.


High-risk profiles for nursing home admission.

A statewide probability sample of 1,625 Massachusetts elderly was studied prospectively over a decade to identify risk profiles for long-term care (LTC) institutionalization. Previous admission to a LTC institution, age, basic ADL disability, and restricted outside mobility were the strongest individual predictors of institutionalization. Examining profiles of risk factors dramatically increased the ability to predict 10-year risk of admission.