A review of the nematode assemblage of the Australian bandicoot, Isoodon macrourus (Peramelidae), from material held in the South Australian Museum with the description of Sprattellus cassonei n. sp. (Mackerrastrongylidae).

A total of 235 vials of nematodes held in the Australian Helminthological Collection of the South Australian Museum from 125 individuals of Isoodon macrourus were examined. The nematode assemblage of I. macrourus, comprising 12 families, including 16 genera and 23 identified species, was compared with the sympatric bandicoot species Perameles nasuta, 20 identified species (Sorensen's index of similarity 0.56) and P. pallescens, 12 identified species (Sorensen's index 0.51). Sprattellus cassonei n. sp. is distinguished from its congeners by having a synlophe with 7-8 ridges with the anterior ventral ridges interrupted, the morphology of the dorsal ray and the branching of the spicule tips. A single male specimen identified as Linstowinema sp. 1. is characterised by seven circles of body hooks, the oesophagus terminating at the level of the seventh circle and robust scale-like spines on the posterior ventral body. A complete description of the species will require additional material, including females. Difficulties in identifying individuals of the genus Mackerrastrongylus to species level are discussed. Overall similarities in the nematode assemblages of the three bandicoot hosts are likely due to shared relationships and similar behaviours.

Heritable anisotropy associated with cognitive impairments among patients with schizophrenia and their non-psychotic relatives in multiplex families.

BACKGROUND: To test the functional implications of impaired white matter (WM) connectivity among patients with schizophrenia and their relatives, we examined the heritability of fractional anisotropy (FA) measured on diffusion tensor imaging data acquired in Pittsburgh and Philadelphia, and its association with cognitive performance in a unique sample of 175 multigenerational non-psychotic relatives of 23 multiplex schizophrenia families and 240 unrelated controls (total = 438). METHODS: We examined polygenic inheritance (h2r) of FA in 24 WM tracts bilaterally, and also pleiotropy to test whether heritability of FA in multiple WM tracts is secondary to genetic correlation among tracts using the Sequential Oligogenic Linkage Analysis Routines. Partial correlation tests examined the correlation of FA with performance on eight cognitive domains on the Penn Computerized Neurocognitive Battery, controlling for age, sex, site and mother's education, followed by multiple comparison corrections. RESULTS: Significant total additive genetic heritability of FA was observed in all three-categories of WM tracts (association, commissural and projection fibers), in total 33/48 tracts. There were significant genetic correlations in 40% of tracts. Diagnostic group main effects were observed only in tracts with significantly heritable FA. Correlation of FA with neurocognitive impairments was observed mainly in heritable tracts. CONCLUSIONS: Our data show significant heritability of all three-types of tracts among relatives of schizophrenia. Significant heritability of FA of multiple tracts was not entirely due to genetic correlations among the tracts. Diagnostic group main effect and correlation with neurocognitive performance were mainly restricted to tracts with heritable FA suggesting shared genetic effects on these traits.

A review and comparison of the nematode assemblages of the Australian golden bandicoot, Isoodon auratus, the quenda, I. fusciventer and southern brown bandicoot, I. obesulus (Peramelidae), from material held in the south Australian museum.

A total of 333 vials of nematodes collected from three species of Isoodon (representing three individuals of I. auratus, 63 of I. fusciventer and 92 of I. obesulus) held in the Australian Helminthological Collection of the South Australian Museum were examined. Nematodes were identified and the nematode assemblages of the three hosts were compared with each other and with the assemblage of Isoodon macrourus. Two fully identified species were recovered from I. auratus, eight from I. fusciventer and 14 from I. obesulus. None of the species occurred in all three hosts; Labiobulura inglisi (Subuluridae), Peramelistrongylus skedastos (Dromaeostrongylidae) and Asymmetracantha tasmaniensis (Mackerrastrongylidae) all occurred in I. fusciventer and I. obesulus. Only Pe. skedastos was also found in I. macrourus. Sorensen's index of similarity, 27.2 %, showed that I. fusciventer and I. obesulus did not have similar nematode communities and neither were their communities similar to that of I. macrourus, 17.1 % and 39.0 % respectively. Labiobulura inglisi and Linstowinema inglisi were the dominant nematodes in the assemblage of I. fusciventer and La. inglisi was dominant in I. obesulus. The two hosts had nematode assemblages with unique species profiles; one species of Linstowinema in I. fusciventer, three in I. obesulus; a species of Physaloptera in I. obesulus, none in I. fusciventer; four species of strongylid; Asymmetracantha tasmaniensis the most prevalent in I. fusciventer, Peramelistrongylus skedastos the most prevalent in I.obesulus. The size of the geographic range is a probable determinant of the species richness of the nematode assemblages.

Persistent infection with neurotropic herpes viruses and cognitive impairment.

BACKGROUND: Herpes virus infections can cause cognitive impairment during and after acute encephalitis. Although chronic, latent/persistent infection is considered to be relatively benign, some studies have documented cognitive impairment in exposed persons that is untraceable to encephalitis. These studies were conducted among schizophrenia (SZ) patients or older community dwellers, among whom it is difficult to control for the effects of co-morbid illness and medications. To determine whether the associations can be generalized to other groups, we examined a large sample of younger control individuals, SZ patients and their non-psychotic relatives (n=1852). Method Using multivariate models, cognitive performance was evaluated in relation to exposures to herpes simplex virus type 1 (HSV-1), herpes simplex virus type 2 (HSV-2) and cytomegalovirus (CMV), controlling for familial and diagnostic status and sociodemographic variables, including occupation and educational status. Composite cognitive measures were derived from nine cognitive domains using principal components of heritability (PCH). Exposure was indexed by antibodies to viral antigens. RESULTS: PCH1, the most heritable component of cognitive performance, declines with exposure to CMV or HSV-1 regardless of case/relative/control group status (p = 1.09 × 10-5 and 0.01 respectively), with stronger association with exposure to multiple herpes viruses (ß = -0.25, p = 7.28 × 10-10). There were no significant interactions between exposure and group status. CONCLUSIONS: Latent/persistent herpes virus infections can be associated with cognitive impairments regardless of other health status.

Glucagon-like peptide-1(9-36)amide metabolite inhibits weight gain and attenuates diabetes and hepatic steatosis in diet-induced obese mice.

AIMS: The metabolic syndrome, a disease arising from the world-wide epidemic of obesity, is manifested as severe insulin resistance, hyperlipidaemia, hepatic steatosis and diabetes. Previously we reported that GLP-1(9-36)amide, derived from the gluco-incretin hormone, glucagon-like peptide-1 (GLP-1), suppresses gluconeogenesis in isolated hepatocytes. The aims of this study were to determine the effects of GLP-1(9-36)amide in diet-induced obese mice that model the development of the metabolic syndrome. METHODS: Mice rendered obese by feeding a very high fat diet were administered GLP-1(9-36)amide via subcutaneous osmopumps for 8 weeks. Body weight, energy intake, plasma insulin and glucose levels (insulin-resistance), and hepatic steatosis were assessed. RESULTS: Eight-week infusions of GLP-1(9-36)amide inhibited weight gain, increased energy intake, prevented the development of fasting hyperinsulinaemia and hyperglycaemia, and curtailed the accumulation of liver triglycerides. The peptide had no effects in mice fed a normal chow diet. Notably, energy intake in the obese mice receiving GLP-1(9-36)amide was 20% greater than obese mice receiving vehicle control. CONCLUSIONS: GLP-1(9-36)amide exerts insulin-like actions in the presence of insulin resistance and prevents the development of metabolic syndrome. Curtailment of weight gain in the face of increased caloric intake suggests that GLP-1(9-36)amide increases energy expenditure. These findings suggest the possibility of the use of GLP-1(9-36)amide, or a peptide mimetic derived there from, for the treatment of obesity, insulin resistance and the metabolic syndrome.

Magellan: initial analysis of venus surface modification.

Initial Magellan observations reveal a planet with high dielectric constant materials exposed preferentially in elevated regions with high slopes, ejecta deposits extending up to 1000 kilometers to the west of several impact craters, windblown deposits and features in areas where there are both obstacles and a source of particulate material, and evidence for slow, steady degradation by atmosphere-surface interactions and mass movements.

Lunar anorthosites.

Sixty-one of 1676 lunar rock fragments examined were found to be anorthosites, markedly different in composition, color, and specific gravity from mare basalts and soil breccias. Compositional similiarity to Tycho ejecta analyzed by Surveyor 7 suggests that the anorthosites are samples of highlands material, thrown to Tranquillity Base by cratering events. A lunar structural model is proposed in which a 25-kilometer anorthosite crust, produced by magmatic fractionation, floats on denser gabbro. Where early major impacts punched through the crust, basaltic lava welled up to equilibrium surface levels and solidified (maria). Mascons are discussed in this context.

Processing of urushiol (poison ivy) hapten by both endogenous and exogenous pathways for presentation to T cells in vitro.

The antigen processing requirements for urushiol, the immunogen of poison ivy (Toxicodendron radicans), were tested by presentation of urushiol to cultured human urushiol-responsive T cells. Urushiol was added to antigen-presenting cells (APC) either before or after fixation with paraformaldehyde. Three distinct routes of antigen processing were detected. CD8+ and CD4+ T cells, which were dependent upon processing, proliferated if urushiol was added to APC before fixation, but did not proliferate when urushiol was added to APC after fixation. Processing of urushiol for presentation to CD8+ T cells was inhibited by azide, monensin, and brefeldin A. This suggests that urushiol was processed by the endogenous pathway. In contrast, presentation of urushiol to CD4+ T cells was inhibited by monensin but not by brefeldin A. This was compatible with antigen processing by the endosomal (exogenous) pathway. Finally, certain CD8+ T cells recognized urushiol in the absence of processing. These cells proliferated in response to APC incubated with urushiol after fixation. Classification of contact allergens by antigen processing pathway may predict the relative roles of CD4+ and CD8+ cells in the immunopathogensis of allergic contact dermatitis.

Induction of hapten-specific tolerance of human CD8+ urushiol (poison ivy)-reactive T lymphocytes.

The interaction of CD28 with B7 molecules (CD80 or CD86) is an essential second signal for both the activation of CD4+ T cells through the T-cell receptor and the prevention of anergy. We studied the requirement of hapten-specific human CD8+ cells for CD28 co-stimulation in recognition of hapten, and anergy induction. Urushiol, the immunogenic hapten of poison ivy (Toxicodendron radicans), elicits a predominantly CD8+ T-cell response. Autologous PBMC were pre-incubated with urushiol prior to fixation by paraformaldehyde. Fixed antigen-presenting cells were unable to present urushiol to human CD8+ urushiol-specific T cells. Addition of anti-CD28, however, overcame this antigen-presenting defect, enabling CD8+ cells to proliferate. Fixation of antigen-presenting cells prevents upregulation of B7, and addition of anti-CD28 substitutes for this signal. Proliferation of CD8+ T cells in response to urushiol was blocked by CTLA4Ig, a recombinant fusion protein that blocks CD28/B7 interactions. Preincubation of urushiol-specific CD8+ cells with fixed PBMC + urushiol for 7 d induced anergy. Anergic CD8+ cells were viable and able to proliferate in response to IL-2, but not in response to urushiol. Induction of anergy required the presence of urushiol, and pre-incubation with irradiated PBMC + urushiol did not have this effect. It is proposed that anergy was induced by presentation of urushiol by fixed PBMC, in the absence of adequate co-stimulation signals. Induction of anergy by blocking of co-stimulation could potentially induce clinical hyposensitization to haptens.

Change in cognitive function in idiopathic Parkinson disease.

OBJECTIVE: To study the effects of Parkinson disease (PD) on cognitive function by determining the frequency and amount of change in Mini-Mental State Examination (MMSE) performance. DESIGN: During a 4-year period, 77 patients with idiopathic PD and 43 normal elders were administered a neuropsychological test battery twice at 2 years apart. RESULTS: A 4-point score difference on the MMSE was the amount that was statistically calculated to be a significant difference at the .05 probability level. Using this metric, 17 (22%) patients with PD had a change in their MMSE performance during a 2-year period. Fifteen individuals performed poorer, and 2 individuals improved. Using the same metric, no normal subjects changed in their MMSE performance. The groups of patients with PD who had a change and did not have a change in their MMSE performance were not characterized by significant differences in their years of education, duration of illness, age at onset, age at test time 1, estimated premorbid intelligence, Hamilton Psychiatric Rating Scale for Depression score at test time I, or Unified Parkinson's Disease Rating Scale score. The singular difference was the higher frequency of change that was found in subjects who were taking dopamine agonists at the second test time. CONCLUSION: A change in cognitive function in patients with PD, as measured by a change of 4 points or more in their MMSE performance, was observed in only 22% of a sample of 77 patients with idiopathic PD during a 2-year period.

Novel glucocorticoid antedrugs possessing a 17beta-(gamma-lactone) ring.

The chemical synthesis and structure-activity relationships of a novel series of 17beta-glucocorticoid butyrolactones possessing either a 16alpha,17alpha-isopropylidene or -butylidene group are described. The sulfur-linked gamma-lactone group was incorporated onto the 17beta-position of the androstane nucleus via Barton ester decarboxylation and trapping the generated 17-radical with butyrolactone disulfides. The glucocorticoid butyrolactones were hydrolyzed in human plasma by the enzyme paraoxonase to the respective hydroxy acids, which were very weak glucocorticoid agonists. The rate of hydrolysis in plasma was very rapid (t1/2 = 4-5 min) in the case of lactones possessing a sulfur atom in the alpha-position of the butyrolactone group, whereas carbon-linked lactones were stable in plasma. 16alpha,17alpha-Butylidenes were more potent glucocorticoid agonists than the corresponding isopropylidene derivatives. Similarly, 1,4-dien-3-ones were more potent than the corresponding 4-en-3-ones. The butyrolactones linked to the steroidal nucleus via the beta-position were more potent glucocorticoid agonists than those linked through the alpha-position of the lactone. The most potent compounds were also shown to be stable in human lung S9 fraction, showed much lower systemic effects than budesonide in the thymus involution test, and possessed topical antiinflammatory activity in the rat ear edema model.

Conditions that enable human hematopoietic stem cell engraftment in all NOD-SCID mice.

BACKGROUND: Transplantation of human hematopoietic stem cells is the only true test of their long-term repopulation potential. Models are readily available to evaluate murine hematopoietic stem cells, but few exist that allow reliable quantification of human stem cells. The non-obese diabetic-severe combined immunodeficient (NOD-SCID) mouse model enables quantification of human hematopoietic stem cells, but the conditions that permit human engraftment in all animals have yet to be defined. The aims of the project were, therefore, to describe the variables that allow human engraftment in the NOD-SCID mouse model and the techniques that accurately quantify this engraftment. METHODS: NOD-SCID mice that had or had not received 250, 325, or 400 cGy irradiation received cord blood (CB) mononuclear or CD34+ cells i.v. or i.p. Mice were killed 6 weeks after transplantation, and the bone marrow, spleen, and thymus were harvested. Four-color flow cytometric analysis, semi-quantitative PCR, myeloid and erythroid progenitor, and stem cell assays were used to monitor human engraftment. RESULTS: A 250 or 325 cGy and i.v. injection of CB mononuclear or CD34+ cells is required to detect multilineage human engraftment in the bone marrow, spleen, or thymus of NOD-SCID mice. Four-color flow cytometric analysis and semi-quantitative PCR enable accurate detection of 0.1% human cells. Progenitor and stem cell assays provide functional information about the engrafted cells. CONCLUSIONS: Successful development of the NOD-SCID mouse model and techniques to assess human engraftment now allow it to be used reliably to analyze the effects of short-term cytokine exposure on the long-term repopulating capacity of CB stem cells.

Pulmonary vascular resistance in emphysema.

To assess the hemodynamic effects of pulmonary microvasculature disruption in emphysema, we examined resting pulmonary hemodynamics and lung function in 12 carefully identified patients with type A chronic obstructive pulmonary disease. Individuals with respiratory muscle weakness and intercurrent infection were excluded. Standard spirometry, helium dilution lung volumes, and single-breath carbon monoxide diffusing capacity (DCOSB) were obtained within 24 h of right heart catheterization. Resistance to pulmonary blood flow was assessed using the difference between pulmonary arterial (PA) diastolic and mean wedge pressures, and expressed as the pulmonary diastolic gradient (PDG). Mean FEV1/FVC was 51 +/- 8 percent, RV/TLC was 48 +/- 11 percent, DCOSB percent predicted was 62 +/- 29 percent, PaO2 was 72 +/- 11 mm Hg (FIO2, 0.21), and PaCO2 was 39 +/- 5 mm Hg. Mean PDG was 5 +/- 3 mm Hg (normal < or = 3 mm Hg) with normal PA pressures, indicating mildly elevated resistance to pulmonary blood flow. The PDG correlated most closely with DCOSB, rising in curvilinear fashion as DCOSB fell (r = -0.869, p < 0.001). These observations were compared with our previous report of analogous findings in patients with chronic, diffuse interstitial lung disease (ILD). In that group, PDG also increased curvilinearly as DCOSB fell (r = -0.839, p < 0.001). Subjects with FVC greater than 50 percent predicted had elevated PDG with normal pressures, while those with FVC less than 50 percent had pulmonary hypertension. The regression of PDG on DCOSB was strikingly similar to emphysema, although the slope in emphysema was less than that in ILD (p < 0.001). These observations suggest that elevated pulmonary vascular resistance in emphysema stems from disruption of the microcirculation in a fashion similar to that encountered in mild-moderate ILD. However, the magnitude of increase is not sufficient to generate resting pulmonary hypertension in the absence of disturbed gas exchange.

Gender and procreation among patients with schizophrenia.

OBJECTIVE: Reduced procreation among men with schizophrenia has been reported consistently when compared with female patients, but the cause is unknown. Reports on Caucasian individuals predominate in the published literature. Therefore, analyses were conducted concurrently among independent Indian and US samples in the present study. METHOD: Individuals with schizophrenia or schizoaffective disorder (DSM-IV criteria) were ascertained and interviewed at New Delhi and in the northeastern United States using identical procedures (n=224 and 144, respectively). Selected indices of fertility and fecundity were compared among men and women at each site. RESULTS: In the smaller US sample, male cases were significantly more likely to be single and childless compared with female cases. They also had fewer children. In contrast, there were no significant gender differences in the larger Indian sample with regard to the reproductive indices. Multivariate analyses revealed that the indices of reproduction were associated with different variables in the US and Indian samples. Fertility (the presence or absence of offspring) was associated with gender and age in the US sample while in the Indian sample conjugal status and age were significant predictors. Fecundity (the number of offspring) was associated with gender, conjugal status and educational status in the US sample while in the Indian sample conjugal status and educational status were both significant. CONCLUSIONS: The reproductive deficit observed among US males was not observed among the Indian men. Conjugal status was a significant covariate for reproduction in both samples. The reproductive deficit may be due to difficulties in establishing long-term conjugal relationships among the US men. The differences may also reflect underlying cultural variations related to marital practices in these two countries. Our analyses suggest that the male reproductive deficit in schizophrenia is variable and may be overcome.

Control of shunt pathway perfusion in diffuse granulomatous lung disease.

To assess the roles of cyclooxygenase inhibition and alveolar hypoxia in controlling the distribution of pulmonary perfusion in granulomatous lung injury, we studied 15 dogs (anesthetized and ventilated) 4 wk after intravenous injection of complete Freund's adjuvant (0.5-0.75 ml/kg). Base-line hemodynamic and blood gas observations were obtained at fractional O2 concentration (FIO2) 0.21 and 0.10. Observations at each FIO2 were repeated 30 min after infusion of meclofenemate (2 mg/kg; n = 10) or saline (n = 5). Resistance to pulmonary blood flow was assessed using the difference between pulmonary arterial diastolic and left atrial pressures (PDG). Distribution of blood flow between normal and diseased regions of the lung was evaluated with measurement of inert gas shunt flow. Before infusion, there were no significant differences between the two groups at either FIO2. At FIO2 0.10 PDG rose from 3 +/- 1 to 7 +/- 3 mmHg in the saline group and from 3 +/- 1 to 8 +/- 3 mmHg in the meclofenemate group, although the shunt flow increased from 8.7 +/- 7.7 to 12.2 +/- 9.2% and from 10.7 +/- 11.0 to 17.6 +/- 18.3 in the two groups, respectively. Saline induced no significant changes at either FIO2. After meclofenemate, PDG at FIO2 0.21 rose to 7 +/- 4 mmHg (P less than 0.015) while shunt flow fell to 5.2 +/- 6.2% (P less than 0.0125), whereas at FIO2 0.10 PDG rose to 15 +/- 5 mmHg (P less than 0.001) while shunt flow rose only to 14.3 +/- 16.4% (P = NS). We propose that perivascular inflammation enhanced perfusion of abnormal lung by elaborating vasodilator prostanoids. By inhibiting prostanoid biosynthesis, meclofenemate selectively increased resistance in diseased lung at FIO2 0.21 and lowered shunt flow. The persistent rise in shunt during hypoxia after meclofenemate suggests that factors other than prostanoids may account for the apparent attenuation of hypoxic vasoconstriction in diseased lung.

Reduction in costs, blood products, and operating time in patients undergoing open heart surgery.

OBJECTIVE: To test the hypothesis that use of aprotinin at hall dose would be more cost-effective or as efficacious as full-dose aprotinin or no aprotinin during open heart surgery. DESIGN: Cost-effective analysis, unmasked prospective comparison. SETTING: Community hospital. PATIENTS: One hundred thirty-three patients undergoing open heart surgery. INTERVENTIONS: Patients in 3 consecutive groups undergoing open heart surgery were allocated to receive no aprotinin, full-dose aprotinin, or half-dose aprotinin. MAIN OUTCOME MEASURES: Total cost (in dollars) of blood products administered plus cost of aprotinin at various dosages, comparison of total blood products administered during hospitalization, and closure time required in the operating room. RESULTS: Full-dose and half-dose aprotinin significantly (P < .05) reduced the total blood products administered during hospitalization and the operating room closure time. However, use of half-dose aprotinin resulted in a significant cost savings (P < .05) when compared with either the cost of blood products required in the nodose aprotinin group or the cost of blood products plus aprotinin in the full-dose aprotinin group. CONCLUSION: Use of aprotinin at half dose in a community hospital resulted in a significant reduction in costs, blood product use, and operating room closure time in patients undergoing open heart surgery.

Late complications of aortic valve replacement with cloth-covered, composite-seat prostheses. A six-year appraisal.

Advanced actuarial techniques are used to analyze early and late results in a closely followed series of 396 patients who received a cloth-covered, composite-seat aortic prosthesis. Late mortality and various complications are carefully assessed, and most late deaths are seen to be unrelated to the prosthesis. One hundred sixteen patients with Model 2310-2320 prostheses who received warfarin postoperatively had no thromboembolic complications in 360 patient-years of follow-up (average, 3.1 years per patient); 134 patients who had the same prosthesis but did not receive warfarin had 9 emboli per 100 patient-years (average follow-up, 1.7 years per patient; total, 228 patient-years). By comparison, in 9 years' experience with non-cloth-covered Model 1200-1260 valves, 132 patients had 4.0 emboli per 100 patient-years (average follow-up, 5.1 years; total, 673 patient-years). The safety of cloth-covered valves is clearly enhanced by concomitant use of anticoagulants; the possibility that antiplatelet drugs may suffice has not yet been demonstrated. Strut cloth wear was found at reoperation in 10 patients. The Model 2400 composite strut ("track") valve with a narrow metal track on the inner surface of each strut prevents this complication.

Long-term survival after postinfarction bypass operation: early versus late operation.

A study of 832 patients operated on within 30 days of infarction from 1974 to 1987 has resulted in 2,388 patient-years (maximum, 14 years) of prospectively acquired follow-up. This study excludes 74 patients in whom cardiogenic shock was the indication for operation. Five-year survival (+/- standard error) was 84% +/- 2%, 85% +/- 1%, and 90% +/- 1%, and 10-year survival was 71% +/- 4%, 68% +/- 1%, and 78% +/- 1% for patients with acute infarction, remote infarction, and no previous infarction, respectively. Age and left ventricular end-diastolic pressure significantly affected long-term survival for patients with acute infarction by both univariate and multivariate analysis. For patients aged less than 65 years, the 5-year and 10-year actuarial survival rates were 89% +/- 2% and 80% +/- 4%, compared with 75% +/- 3% and 58% +/- 9%, respectively, for patients aged more than 65 years. The survival percentages were 89% +/- 2% and 75% +/- 6% for patients with left ventricular end-diastolic pressure less than 15 mm Hg compared with 77% +/- 5% and 67% +/- 7% for patients with left ventricular end-diastolic pressure greater than 15 mm Hg. Operative mortality was 7.6% for patients operated on within 24 hours, compared with 4.1% for patients operated on between 2 and 30 days after infarction. Ten-year survival was similar (about 70%) for all timing groups. Based on these long-term results, there appears to be little to gain by delaying coronary artery bypass grafting, when indicated, after infarction occurs.

Cytokine indices in Alzheimer's temporal cortex: no changes in mature IL-1 beta or IL-1RA but increases in the associated acute phase proteins IL-6, alpha 2-macroglobulin and C-reactive protein.

Recent immunocytochemical data have demonstrated increases in interleukin-1 beta (IL-1 beta), interleukin-6 (IL-6) and the IL-6-inducible acute phase protein, alpha 2-macroglobulin (alpha 2-M), in Alzheimer's disease (AD) brains. We investigated the levels of these proteins quantitatively using ELISA procedures and determined if increases in IL-1 beta were compensated for by a parallel increase in the endogenous interleukin-1 receptor antagonist (IL-1RA). Comparing control vs. Alzheimer's temporal cortex, we examined mature IL-1 beta, IL-1RA, IL-6, alpha 2-M and C-reactive protein (CRP). The specificities of the ELISA procedures were verified by serial dilutions of the samples; by chromatofocusing, and by Sephadex G-150 gel filtration. There were no differences in the levels of mature IL-1 beta or IL-1RA in AD and control brains. However, IL-6 levels were detectable in 14 of the 16 Alzheimer samples but only 2 of the 14 control samples. There were also significant increases seen in alpha 2-M and CRP levels in the Alzheimer's group compared to controls. These data support previous studies demonstrating a possible up-regulation of neuroimmune function in Alzheimer's cortex; however, we cannot determine, at this time, if this immune reaction is initiated by IL-1 beta.