Acute kidney injury requiring dialysis secondary to adenovirus nephritis in renal transplant recipient.

Disseminated adenoviral infection is a serious problem, especially in an immunocompromised host. The disease carries a mortality rate reaching as high as 80%. It is seen most frequently in bone marrow transplant recipients, where it causes pneumonia and disseminated disease. In solid organ transplant recipients it causes graft infection. We report the case of a renal transplant recipient with disseminated adenoviral infection and acute kidney failure requiring dialysis. Reduction of immunosuppression and 1 dose of cidofovir were associated with resolution of viremia and viruria and return of kidney function to near baseline.

Molecular structures and interactions in the yeast kinetochore.

Kinetochores are the elaborate protein assemblies that attach chromosomes to spindle microtubules in mitosis and meiosis. The kinetochores of point-centromere yeast appear to represent an elementary module, which repeats a number of times in kinetochores assembled on regional centromeres. Structural analyses of the discrete protein subcomplexes that make up the budding-yeast kinetochore have begun to reveal principles of kinetochore architecture and to uncover molecular mechanisms underlying functions such as transmission of tension and establishment and maintenance of bipolar attachment. The centromeric DNA is probably wrapped into a compact organization, not only by a conserved, centromeric nucleosome, but also by interactions among various other DNA-bound kinetochore components. The rod-like, heterotetrameric Ndc80 complex, roughly 600 Å long, appears to extend from the DNA-proximal assembly to the plus end of a microtubule, to which one end of the complex is known to bind. Ongoing structural studies will clarify the roles of a number of other well-defined complexes.

Visualizing levels of osteoblast differentiation by a two-color promoter-GFP strategy: Type I collagen-GFPcyan and osteocalcin-GFPtpz.

A 3.9 kb DNA fragment of human osteocalcin promoter and 3.6 kb DNA fragment of the rat collagen type1a1 promoter linked with visually distinguishable GFP isomers, topaz and cyan, were used for multiplex analysis of osteoblast lineage progression. Three patterns of dual transgene expression can be appreciated in primary bone cell cultures derived from the transgenic mice and by histology of their corresponding bones. Our data support the interpretation that strong pOBCol3.6GFPcyan alone is found in newly formed osteoblasts, while strong pOBCol3.6GFPcyan and hOC-GFPtpz are present in osteoblasts actively making a new matrix. Osteoblasts expressing strong hOC-GFPtpz and weak pOBCol3.6GFPcyan are also present and may or may not be producing mineralized matrix. This multiplex approach reveals the heterogeneity within the mature osteoblast population that cannot be appreciated by current histological methods. It should be useful to identify and isolate populations of cells within an osteoblast lineage as they progress through stages of differentiation.

Structural basis for the insensitivity of a serine enzyme (palmitoyl-protein thioesterase) to phenylmethylsulfonyl fluoride.

Palmitoyl-protein thioesterase-1 (PPT1) is a newly described lysosomal enzyme that hydrolyzes long chain fatty acids from lipid-modified cysteine residues in proteins. Deficiency in this enzyme results in a severe neurodegenerative storage disorder, infantile neuronal ceroid lipofuscinosis. Although the primary structure of PPT1 contains a serine lipase consensus sequence, the enzyme is insensitive to commonly used serine-modifying reagents phenylmethylsulfonyl fluoride (PMSF) and diisopropylfluorophosphate. In the current paper, we show that the active site serine in PPT1 is modified by a substrate analog of PMSF, hexadecylsulfonylfluoride (HDSF) in a specific and site-directed manner. The apparent K(i) of the inhibition was 125 micrometer (in the presence of 1.5 mm Triton X-100), and the catalytic rate constant for sulfonylation (k(2)) was 3.3/min, a value similar to previously described sulfonylation reactions. PPT1 was crystallized after inactivation with HDSF, and the structure of the inactive form was determined to 2.4 A resolution. The hexadecylsulfonyl was found to modify serine 115 and to snake through a narrow hydrophobic channel that would not accommodate an aromatic sulfonyl fluoride. Therefore, the geometry of the active site accounts for the reactivity of PPT1 with HDSF but not PMSF. These observations suggest a structural explanation as to why certain serine lipases are resistant to modification by commonly used serine-modifying reagents.

The crystal structure of palmitoyl protein thioesterase 1 and the molecular basis of infantile neuronal ceroid lipofuscinosis.

Mutations in palmitoyl-protein thioesterase 1 (PPT1), a lysosomal enzyme that removes fatty acyl groups from cysteine residues in modified proteins, cause the fatal inherited neurodegenerative disorder infantile neuronal ceroid lipofuscinosis. The accumulation of undigested substrates leads to the formation of neuronal storage bodies that are associated with the clinical symptoms. Less severe forms of PPT1 deficiency have been found recently that are caused by a distinct set of PPT1 mutations, some of which retain a small amount of thioesterase activity. We have determined the crystal structure of PPT1 with and without bound palmitate by using multiwavelength anomalous diffraction phasing. The structure reveals an alpha/beta-hydrolase fold with a catalytic triad composed of Ser115-His289-Asp233 and provides insights into the structural basis for the phenotypes associated with PPT1 mutations.

Stereotypical beliefs about overweight and smoking and decision-making in assignments to sales territories.

This study examined job bias associated with business students' role-playing as sales managers who assigned trainees to sales territories. Personal characteristics of being extremely overweight and being a heavy smoker were studied. Research participants were given a personnel record (training record) of a sales trainee and asked to make a sales territory assignment decision; three vacant territories were also described. The participants were told to assign the trainee to one of the territories or to indicate a preference to not have the recruit assigned to any territory within the role-playing manager's region. Analysis indicates that a sales recruit described as extremely overweight was less likely to be assigned to an important or desirable sales territory and more likely to be assigned to an undesirable territory or not selected at all for an assignment within a sales region. Those described as heavy smokers were similarly treated but to a lesser degree. Overweight saleswomen were discriminated against more than overweight salesmen.

Differences between consumers and psychiatrists in attitude toward advertising of psychiatric services.

Psychiatrist and consumer attitudes toward the advertising of psychiatric services are examined. The results indicate that consumers are consistently more favorable than psychiatrists toward psychiatric services advertising. Both groups felt that professional magazines are the most appropriate media for psychiatrists who advertise. The psychiatrists reported a higher level of exposure to advertising of psychiatric services than did the consumers. However, some apprehension about psychiatric services advertising also was reported. Managerial implications for advertising usage by the practicing psychiatrist are presented.

Consumer versus dentist attitudes toward dental services advertising.

The authors report the findings of a consumer survey and a dentist survey that were used to examine attitudes toward the advertising of dental services. The results clearly indicate positive consumer attitudes and negative dentist attitudes toward such advertising. Relatively few consumer demographic differences are noted, though younger dentists appear to have more positive attitudes toward dental services advertising than their older colleagues. The results suggest significant opportunities for dentists in dental services advertising.

Low dose perphenazine and levodopa/carbidopa therapy in a patient with Parkinsonism and a psychotic illness.

Psychological morbidity is a common consequence of both Parkinson's disease and its treatment with antiparkinsonian agents. The authors describe an unusual case of a patient with Parkinson's disease and a psychosis who was treated with levodopa/carbidopa and very low dose perphenazine. The case raises the issue whether patients with profound psychological reactions to antiparkinson agents may be maintained on antiparkinsonian therapy by the addition of phenothiazines.