Age effects on executive ability

Heterogeneity of executive tasks has made it difficult to determine whether there are age-related declines in executive functioning. To address this issue, 112 individuals, 20-79 years old, took the California Trail Making Test (CTMT) and the California Stroop Test (CST), subtests of the Delis-Kaplan Executive Function Scale (D. C. Delis, E. Kaplan, & J. H. Kramer, in press) that include measurement of component skills embedded in the executive function tasks. Multiple regression analyses revealed that after controlling for component skills, age had a significant effect on the executive requirement of the CST, namely speed on the interference condition. Age did not affect switching performance on the letter-number condition of the CTMT. Additional analyses revealed that age was significantly associated with commission of certain types of errors. This study confirms the importance of partialing out components in the assessment of multidimensional cognitive tasks, particularly when making age comparisons. It also emphasizes specificity over generalizability when examining the impact of age on cognition.     

Evaluation of the Spot-CAMP test for the rapid presumptive identification of group B streptococci

A rapid Spot-CAMP test was evaluated for its ability to accurately identify colonies of Streptococcus agalactiae (Lancefield Group B) growing on primary sheep blood agar plates. The test uses a beta-lysin-containing filtrate, which is prepared from a broth culture of Staphylococcus aureus. A drop of beta-lysin filtrate is applied adjacent to a suspected group B Streptococcus (GBS) colony and the plate is incubated and then examined for a zone of synergistic hemolysis. The Spot-CAMP test demonstrated 100% correlation with both a Standard CAMP procedure and Lancefield serogrouping. The rapid Spot-CAMP test was easy to perform and inexpensive, and could presumptively identify within 30 minutes colonies of GBS growing on primary isolation plates.     

Rescue of a thymotropic, leukemogenic C-type virus from cultured, nonproducer-lymphoma cells of strain C57BL/Ka mice.

A permanent cell line, BL/RL₁₂-NP, derived from a radiation-induced C57BL/Ka mouse lymphoid tumor, has remained devoid of MuLV expression, except for the rare, sporadic initiation of virus production in some cultures. It can, however, be stably infected by the radiation leukemia virus (RadLV), and the progeny virus population retains the biological and serological properties of the parental RadLV. The cells can also be infected by a B-ecotropic, nonthymotropic, nonleukemogenic C57BL/Ka virus isolate, BL/Ka (B). In the latter situation, the emerging virus particles may exhibit thymotropic and leukemogenic (T+L+) attributes similar to those of RadLV, while retaining at least some of the envelope determinants of BL/Ka (B). These observations suggest that, following productive infection by a nonleukemogenic helper virus, oncogenic sequences endogenous to the non-producer lymphoma cells may be packaged in infectious progeny virions. The data are interpreted as providing strong support for the existence, in radiogenic lymphomas, of defective T+L+ sequences, designated RadLV-O. Possible mechanisms whereby RadLV-O is later expressed as an infectious leukemogenic virus are discussed.     

Inhibition of host resistance by nutritional hypercholesteremia.

Previous experiments showed that nutritionally induced hypercholesteremia in mice caused an increase in susceptibility to coxsackievirus B, with a marked suppression of cellular infiltrates in infected tissues and an increased mortality. The present studies demonstrated that a hypercholesteremic diet was associated with an inhibition in host resistance as measured by susceptibility to Listeria monocytogenes infection and the growth of two transplanted syngeneic murine tumors. Moreover, the ability of Corynebacterium parvum to induce regression of a transplanted methylcholanthrene-induced fibrosarcoma was inhibited in hypercholesteremic hosts, as was the histiocytic infiltration normally accompanying C. parvum inoculation. In contrast, the peritoneal macrophages from C. parvum-treated hypercholesteremic mice were indistinguishable from similarly treated macrophages from normal mice with respect to their in vitro tumoricidal activity and the presence of a cell surface antigen associated with activated macrophages. Hypercholesteremia was also associated with a decreased antibody response to sheep erythrocytes in vivo, but dit not appear to exert a detrimental effect on B- or T-cell blastogenesis when tested in vitro. The findings that the hypercholesteremic diet was associated with an impairment in the host immune response and increased susceptibility to viral, bacterial, and tumor cell challenge are discussed with respect to virus-lipid interactions in the pathogenesis of atherogenesis and diabetes mellitus.     

A prospective trial of colchicine for primary biliary cirrhosis

We entered 60 patients with primary biliary cirrhosis in a double-blind randomized controlled trial to determine whether colchicine is therapeutically effective. Thirty patients had early disease (Stages 1 and 2), and 30 had advanced disease (Stages 3 and 4). Fifteen patients with early disease and 15 with advanced disease received colchicine (0.6 mg twice daily), and the remainder received placebo. Patients were studied about every two months; those remaining in the blind phase at two years underwent repeat liver biopsy and were then placed on open-label colchicine (0.6 mg twice daily). With a few exceptions, the results in patients with early disease were similar to those in patients with advanced disease; hence, data on patients in all stages were combined in the main analysis. During the two-year study period the colchicine-treated patients, as compared with the placebo-treated patients, had improvement in levels of serum albumin, serum bilirubin, alkaline phosphatase, cholesterol, and aminotransferases. However, there was no such improvement in the severity of symptoms or physical findings; moreover, there was no significant difference in the histologic changes noted at liver biopsy in the two treatment groups. At four years after entry, the cumulative mortality from liver disease was 21 percent in patients given colchicine and 47 percent in those given placebo (P = 0.05). The only side effect of colchicine was diarrhea, noted in three patients. The consistent and significant improvement in a number of markers of liver disease and the apparent decreased mortality from liver disease suggest that colchicine may provide some long-term clinical benefit in patients with primary biliary cirrhosis. However, the failure of colchicine to reduce hepatic inflammation and fibrosis leaves uncertain the effect of the drug on the longterm outcome of this disease.     

Refined genetic mapping of autosomal recessive chronic distal spinal muscular atrophy to chromosome 11q13.3 and evidence of linkage disequilibrium in European families

Chronic distal spinal muscular atrophy (Chronic DSMA, MIM (*)607088) is a rare autosomal recessive disorder characterized by a progressive motor weakness and muscular atrophy, predominating in the distal parts of the limbs. A form of Chronic DSMA gene has been previously mapped to chromosome 11q13 in the 10.3 cM interval defined by loci D11S1889 and D11S1321. By linkage analysis in 12 European Chronic DSMA families, we showed that a disease gene maps to chromosome 11q13.3 (Z(max)=6.66 at theta=0.00 at the DSM4 locus) and suggested that this condition is genetically homogeneous. Recombination events allowed us to reduce the genetic interval to a 2.6 cM region, telomeric to the IGHMBP2 gene, excluding this gene as the disease causing gene in Chronic DSMA. Moreover, partial linkage disequilibrium was found between three rare alleles at loci D11S1369, DSM4 and D11S4184 and the mutant chromosome in European patients. Analysis of the markers at these loci strongly suggests that most Chronic DSMA chromosomes are derived from a single ancestor. Refinement of the Chronic DSMA locus will hopefully allow to test candidate genes and lead to identification of the disease-causing mutations.     

Hemolytic uremic syndrome with hypocomplementemia, serum C3NeF, and glomerular deposits of C3

A 4-year-old boy had hemolytic uremic syndrome (HUS) associated with depression of serum C3 level, a B-hemolytic streptococcal throat infection, and an elevated level of antistreptolysin O titer. In addition to the characteristic histologic changes associated with this syndrome, substantial infiltration of polymorphonuclear leukocytes and nodular deposits of C3 globulin were seen in the glomeruli of the first biopsy specimen. Two months after clinical remission, he had a recurrence of hemolytic anemia, thrombocytopenia, and acute renal failure. The serum C3 concentration had decreased again, and serum C3NeF was detected in the serum. The typical changes associated with HUS were still present on electron microscopy. Bilateral nephrectomy and renal transplantation were done because of the development of uncontrollable severe hypertension and increasing azotemia. This patient had three manifestations of HUS, but because of several differences, such as hypocomplementemia, serum C3NeF, a recurrence, and persistent glomerular deposits of C3 globulin, he appears to have had a different form of the syndrome.     

Maturation of Startle Modulation

This study of the maturation of prestimulation-induced modulation of startle in 3 to 8 year old children and adults demonstrated significant effects of age on both startle magnitude and onset latency. Startle was evoked by 104dB(SPL) 50-ms bursts of white noise, and the amplitude and onset latency of the blink reflex were measured after integration of the obicularis oculi EMG. Prestimulation with 75dB 1000 Hz tones resulted in severe inhibition of both amplitude and latency in adults when 20-ms tones preceded the startling stimuli by 120 ms or 250 ms. Following sustained prestimulation for 2000 ms, the adults showed modest nonsignificant response facilitation. Eight-year-old children showed mature inhibitory and facilitatory startle amplitude modulation, but significantly less inhibition and more facilitation of onset latency compared to adults. Preschool children showed significantly less amplitude and latency inhibition and more facilitation than 8-year-olds and adults. In response to prestimulation 120 ms before startling stimuli, the preschool children actually showed latency facilitation. Modulation of startle by prestimulation is mediated by brainstem neuronal networks. These findings suggest that brainstem mechanisms which mediate startle response modulation undergo development during early childhood and do not mature until about 8 years of age.     

Quantitative assays of pharmacologic aerosols used in studying asthma

To more nearly accurately quantitate the dose of pharmacologic agents delivered to human and animal airways via aerosols, we have developed a monodisperse aerosol containing either methacholine or histamine that permits a light scattering device (tyndallometry) to measure accurately the quantity of inspired and expired particles. These aerosols (described in previous studies) are simultaneously tagged with a radioactive label (technetium 99m) to permit the use of external gamma camera imaging. Present work focuses on the development of assay techniques to measure the quantity of methacholine delivered in these aerosols. The lack of specific radioimmune or radioenzyme assays coupled with the cross-reaction of organic contaminants with conventional chemical reagents for measuring methacholine required the development of separative techniques to isolate the methacholine from the organic aerosol contaminants. With aqueous extraction and column separation we have been able to completely isolate the methacholine from these contaminants. This allows the application of standard spectrophotometric assays for methacholine to quantitate the methacholine in the resulting solution. These separative techniques will permit the use of these aerosols in quantitative studies of airway reactivity.