The structure of depression among elderly institution residents: affective and somatic correlates of physical frailty

BACKGROUND: Confounding of depression with somatic illness and anxiety, a problem in any age group, may be especially troublesome in frail older persons. This paper examined this problem in a factor analytic study of the structure of depressive symptomatology, identifying affective and somatic symptom clusters and relating those clusters to health and functional variables cross-sectionally and prospectively over a 1-year interval. METHODS: The factor structure of a DSM-IV symptom checklist was examined among 1,245 elderly long-term care residents. Regression analyses examined the association of resulting factors with cognition, functional disability, self- and physician-rated health, and pain at baseline and a year later. One-year mortality was also examined. RESULTS: Factor analysis revealed three unique symptom clusters: depressed mood, somatic symptoms, and psychic anxiety. Depressed mood and somatic symptoms were associated cross-sectionally with all functional health variables, but psychic anxiety was associated only with pain. Longitudinally, depressed mood was the only independent predictor of decline in cognition, functional ability, physician-rated health, and mortality; the last effect, however, did not withstand control for baseline health and functioning. Somatic symptoms at baseline predicted decrement in self-rated health a year later. Effects varied as a function of cognitive status. CONCLUSIONS: These data suggest that concerns about the confounding role of somatic symptoms in the association of depression with physical health are unfounded. Although somatic symptoms of depression and anxiety were associated with health and functional status cross-sectionally, depressed mood was by far the stronger predictor of health declines over time.     

The Eek receptor, a member of the Eph family of tyrosine protein kinases, can be activated by three different Eph family ligands

The Eph family of receptors, the largest subgroup within the tyrosine protein kinase receptor family, are comprised of at least thirteen members, many of which are predominantly expressed in the developing and adult nervous system. In this study, we have isolated a full-length cDNA, encoding the mouse homologue of a previous partially characterized Eek protein, a member of Eph receptor tyrosine kinase family. In a comparison of the amino acid sequences of various Eph family members, Eek is most similar to Ehk-3/MDK1, Sek/Cek8, Ehk-2, Hek/Mek4/Cek4, and Bsk/Ehk1/Rek7/Cek7, which are predominantly expressed in the nervous system. Additionally, we have used a low-stringency PCR cloning technique to identify ligands, related to B61, that may interact with Eek. Three different GPI-linked ligands, namely Elf-1/Cek7-L, Ehk1-L/Efl-2/Lerk3 and AL-1/RAGS, were isolated from mouse brain. To study the functional interactions between these ligands and the Eek receptors, we have constructed chimeric ligands consisting of the Fc portion of human IgG fused to their carboxyl-terminus. These chimeric ligands bound to, and activated both the Eek receptors and the Eek-TrkB chimeric receptors expressed in NIH3T3 cells. These findings suggest that Eek receptor can be activated by at least three different GPI-linked ligands.     

Protein kinase A-anchoring inhibitor peptides arrest mammalian sperm motility

Cyclic AMP-dependent protein kinase (PKA) is anchored at specific subcellular sites through the interaction of the regulatory subunit (R) with protein kinase A-anchoring proteins (AKAPs) via an amphipathic helix binding motif. Synthetic peptides containing this amphipathic helix domain competitively disrupt PKA binding to AKAPs and cause a loss of PKA modulation of cellular responses. In this report we use S-Ht31, a cell-permeant anchoring inhibitor peptide, to study the role of PKA anchoring in sperm. Our analysis of three species of mammalian sperm detected three isoforms of PKA (RIIalpha, RIIbeta, and RIbeta) and one 110-kDa AKAP. The addition of S-Ht31 to bovine caudal epididymal sperm inhibits motility in a time- and concentration-dependent manner. A control peptide, S-Ht31-P, identical to S-Ht31 except for a proline for isoleucine substitution to prevent amphipathic helix formation, had no effect on motility. The inhibition of motility by S-Ht31 is reversible but only if calcium is present in the suspension buffer, suggesting a role for PKA anchoring in regulating cellular calcium homeostasis. Surprisingly, inhibition of PKA catalytic activity had little effect on basal motility or motility stimulated by agents previously thought to work via PKA activation. These data suggest that the interaction of the regulatory subunit of PKA with sperm AKAPs, independent of PKA catalytic activity, is a key regulator of sperm motility and that disruption of this interaction using cell-permeable anchoring inhibitor peptides may form the basis of a sperm-targeted contraceptive.     

Restriction fragment length polymorphism analysis reveals different allele frequency and a linkage disequilibrium at locus D1S94 in neuroblastoma patients

Deletion of chromosome 1p and MYCN amplification have been reported as frequent abnormalities in human neuroblastoma. We studied loss of heterozygosity (LOH) in 50 (48 informative) Italian neuroblastoma patients by restriction fragment length polymorphisms (RFLPs) analysis using anonymous and hypervariable region (HVR) sequences. Twelve cases (25%) showed LOH at one or more loci. Locus D1S94 was the most frequently involved in LOH events (8/12) of deleted cases (66.6%). MYCN amplification was observed in 20% of patients which showed a significantly lower event-free survival probability (EFSp) (P = 0.004). We also studied the allelic distribution in the constitutional DNA of neuroblastoma patients (n = 44) and a matched group of healthy Italian subjects (n = 79) for loci D1S112 and D1S94. A significantly (P = 0.01) different allele frequency was detected for the two groups at locus D1S94, but not at D1S112. Moreover, the neuroblastoma population did not confirm the Hardy-Weinberg expectations at the former locus. This observation suggests the existence of an allelotype associated with neuroblastoma susceptibility.     

Surface charge of bacteriorhodopsin detected with covalently bound pH indicators at selected extracellular and cytoplasmic sites

We present a method that allows the detection of the surface charge density of bacteriorhodopsin (bR) at any selected protein surface site. The optical pH indicator fluorescein was covalently bound to the sulfhydryl groups of single cysteine residues, which were introduced at selected positions in bR by site-directed mutagenesis. On the extracellular side, the positions were in the BC loop (72) and in the DE loop (129-134). On the cytoplasmic side, one position in each loop was labeled: 35 (AB), 101 (CD), 160 (EF), and 231 (carboxy tail). The apparent pKs of fluorescein in these positions were determined for various salt concentrations. The local surface charge density was calculated from the dependence of the apparent pK of the dye on the ionic strength using the Gouy-Chapman equation. The surface charge density at pH 6.6 is more negative on the cytoplasmic side (averaged over all positions, -2.5 +/- 0.2 elementary charges per bR) than on the extracellular side (average, -1.8 +/- 0.2 elementary charges per bR) with little variation along the surface. Since the experiments were performed with electrically neutral CHAPS/DMPC micelles, these values represent the charge present on bR itself.(ABSTRACT TRUNCATED AT 250 WORDS)     

Wound seeding associated with endometrial cancer

We report a patient with well-differentiated adenocarcinoma of the endometrium who developed a recurrence in the anterior abdominal wall probably secondary to wound seeding at the time of her original surgery. She underwent total abdominal hysterectomy, bilateral salpingo-oophorectomy. She then received 15 mCi of 32P for positive peritoneal washings. She was free of disease until 2 years later when a large lower incision mass developed. She had no evidence for intra-abdominal disease and a radical resection with a myocutaneous flap was undertaken. Radical resection for isolated metastases may be of benefit for patients with endometrial cancer. Patients with positive cytology should be observed closely for incisional recurrence.     

Correlation between structure and magnetic spin state of the manganese cluster in the oxygen-evolving complex of photosystem II in the S2 state: determination by X-ray absorption spectroscopy

The structure of the manganese cluster in the S2 state with the g approximately 4 EPR signal (S2-g4 state) generated by 130 K illumination of photosystem II (PSII) membranes prepared from spinach has been investigated by X-ray absorption spectroscopy. The Mn X-ray absorption K-edge spectra of the S2-g4 state not only show a shift of the inflection point to higher energy from the S1 state but also reveal a different edge shape from that of the S2 state with the multiline signal (S2-MLS state). Extended X-ray absorption fine structure (EXAFS) studies of the Mn K-edge show that the structure of the Mn cluster in the S2-g4 state is distinctly different from those in the S2-MLS or S1 states. In the S2-g4 state, the second shell of back-scatters from the Mn absorber is found to contain two Mn-Mn distances of 2.73 and 2.85 A. We interpret this to indicate the presence of two nonequivalent di-mu-oxo-bridged Mn binuclear structures in the Mn cluster of the S2-g4 state. The third shell of the S2-g4 state at about 3.3 A also contains increased heterogeneity. By contrast, very little distance disorder was found to exist in the second shell of the S1 or S2-MLS states. A mechanism is proposed to explain these results in the context of our model for the Mn cluster and the EPR properties of the Mn complex in the S2 state.     

Larvicidal activity of the entomopathogenic fungus Tolypocladium cylindrosporum (Deuteromycotina: Hyphomycetes) on the mosquito Aedes triseriatus and the black fly Simulium vittatum (Diptera: Simuliidae)

Laboratory bioassays evaluated the pathogenicity of the entomopathogenic fungus Tolypocladium cylindrosporum against Aedes triseriatus. All larval instars were found to be susceptible at temperatures from 18 to 25 degrees C. Blastoconidia were more virulent than conidia. Mortality was proportional to exposure time in assays using blastoconidia. Blastoconidia and exposure time appear to be a more adequate method for bioassay of T. cylindrosporum virulence than the standard procedure of using conidia and continuous exposure. Tolypocladium cylindrosporum was also active against Simulium vittatum black fly larvae, but the mortality recorded was much lower than with mosquito larvae.