First Study of the

New astronomical observations point to a nucleosynthesis picture that goes beyond what was accepted until recently. The intermediate "i" process was proposed as a plausible scenario to explain some of the unusual abundance patterns observed in metal-poor stars. The most important nuclear physics properties entering i-process calculations are the neutron-capture cross sections and they are almost exclusively not known experimentally. Here we provide the first experimental constraints on the ^{139}Ba(n,γ)^{140}Ba reaction rate, which is the dominant source of uncertainty for the production of lanthanum, a key indicator of i-process conditions. This is an important step towards identifying the exact astrophysical site of stars carrying the i-process signature.

A comprehensive phylogeny helps clarify the evolutionary history of host breadth and lure response in the Australian Dacini fruit flies (Diptera: Tephritidae).

The tribe Dacini (Diptera: Tephritidae) contains over 930 recognised species and has been widely studied due to the economic importance of some taxa, such as the Oriental fruit fly Bactrocera dorsalis. Despite the attention this group has received, very few phylogenetic reconstructions have comprehensively sampled taxa from a single biogeographic region, thereby limiting our capacity to address more targeted evolutionary questions. To study the evolution of diet breadth and male lure response, two key traits fundamental to understanding dacine diversity and the biology of pest taxa, we analysed 273 individuals representing 144 described species from Australia (80% continental coverage), the Pacific, and select close relatives from South-east Asia to estimate a dated molecular phylogenetic reconstruction of the Dacini. We utilised seven loci with a combined total of 4,332 nucleotides, to estimate both Bayesian and Maximum Likelihood phylogenies of the tribe. Consistent with other molecular phylogenies of the tribe, there was a high level of disagreement between the placement of species in the phylogeny and their current subgeneric and species-complex level taxonomies. The Australian fauna exhibit high levels of endemism, with radiations of both exclusively Australian clades, and clades that originate elsewhere (e.g. the Bactrocera dorsalis species group). Bidirectional movement of species has occurred between Papua New Guinea and Australia, with evidence for multiple incursions over evolutionary time. The Bactrocera aglaiae species group emerged sister to all other Bactrocera species examined. Divergence time estimates were âˆ¼ 30 my younger than previously reported for this group, with the tribe diverging from its most recent common ancestor âˆ¼ 43 mya. Ancestral trait reconstruction and tests for trait phylogenetic signal revealed a strong signal for the evolution of male lure response across the tree, with cue-lure/raspberry ketone lure response the ancestral trait. Methyl eugenol response has arisen on multiple, independent occasions. The evolution of host breadth exhibited a weaker signal; yet, basal groups were more likely to be host specialists. Both the evolution of lure response and host fruit use provide predictive information for the outbreak management of understudied pest fruit flies for which direct inference of these features may be lacking. Our results, which parallel those of earlier research into the closely-related African Dacus spp., demonstrate how geographically focussed taxon coverage allows Dacini phylogenetics to more explicitly test evolutionary hypotheses, thereby progressing our understanding of the evolution of this highly diverse and recently-radiated group of flies.

Polytrauma and High-energy Injury Mechanisms are Associated with Worse Patient-reported Outcomes After Distal Radius Fractures.

BACKGROUND: Patient-reported outcomes (PROs) are increasingly relevant when evaluating the treatment of orthopaedic injuries. Little is known about how PROs may vary in the setting of polytrauma or secondary to high-energy injury mechanisms, even for common injuries such as distal radius fractures. QUESTIONS/PURPOSES: (1) Are polytrauma and high-energy injury mechanisms associated with poorer long-term PROs (EuroQol Five Dimension Three Levels [EQ-5D-3L] and QuickDASH scores) after distal radius fractures? (2) What are the median EQ-5D-3L, EQ-VAS [EuroQol VAS], and QuickDASH scores for distal radius fractures in patients with polytrauma, high-energy monotrauma and low-energy monotrauma METHODS: This was a retrospective study with followup by questionnaire. Patients treated both surgically and conservatively for distal radius fractures at a single Level 1 trauma center between 2008 and 2015 were approached to complete questionnaires on health-related quality of life (HRQoL) (the EQ-5D-3L and the EQ-VAS) and wrist function (the QuickDASH). Patients were grouped according to those with polytrauma (Injury Severity Score [ISS] ≥ 16), high-energy trauma (ISS < 16), and low-energy trauma based on the ISS score and injury mechanism. Initially, 409 patients were identified, of whom 345 met the inclusion criteria for followup. Two hundred sixty-five patients responded (response rate, 77% for all patients; 75% for polytrauma patients; 76% for high-energy monotrauma; 78% for low-energy monotrauma (p = 0.799 for difference between the groups). There were no major differences in baseline characteristics between respondents and nonrespondents. The association between polytrauma and high-energy injury mechanisms and PROs was assessed using forward stepwise regression modeling after performing simple bivariate linear regression analyses to identify associations between individual factors and PROs. Median outcome scores were calculated and presented. RESULTS: Polytrauma (intraarticular: ß -0.11; 95% confidence interval [CI], -0.21 to -0.02]; p = 0.015) was associated with lower HRQoL and poorer wrist function (extraarticular: ß 11.9; 95% CI, 0.4-23.4; p = 0.043; intraarticular: ß 8.2; 95% CI, 2.1-14.3; p = 0.009). High-energy was associated with worse QuickDASH scores as well (extraarticular: ß 9.5; 95% CI, 0.8-18.3; p = 0.033; intraarticular: ß 11.8; 95% CI, 5.7-17.8; p < 0.001). For polytrauma, high-energy trauma, and low-energy trauma, the respective median EQ-5D-3L outcome scores were 0.84 (range, -0.33 to 1.00), 0.85 (range, 0.17-1.00), and 1.00 (range, 0.174-1.00). The VAS scores were 79 (range, 30-100), 80 (range, 50-100), and 80 (range, 40-100), and the QuickDASH scores were 7 (range, 0- 82), 11 (range, 0-73), and 5 (range, 0-66), respectively. CONCLUSIONS: High-energy injury mechanisms and worse HRQoL scores were independently associated with slightly inferior wrist function after wrist fractures. Along with relatively well-known demographic and injury characteristics (gender and articular involvement), factors related to injury context (polytrauma, high-energy trauma) may account for differences in patient-reported wrist function after distal radius fractures. This information may be used to counsel patients who suffer a wrist fracture from polytrauma or high-energy trauma and to put their outcomes in context. Future research should prospectively explore whether our findings can be used to help providers to set better expectations on expected recovery. LEVEL OF EVIDENCE: Level III, therapeutic study.

Patterns of cryptic host specificity in duck lice based on molecular data.

Documenting patterns of host specificity in parasites relies on the adequate definition of parasite species. In many cases, parasites have simplified morphology, making species delimitation based on traditional morphological characters difficult. Molecular data can help in assessing whether widespread parasites harbour cryptic species and, alternatively, in guiding further taxonomic revision in cases in which there is morphological variation. The duck louse genus Anaticola (Phthiraptera: Philopteridae), based on current taxonomy, contains both host-specific and widespread species. Mitochondrial and nuclear DNA sequences of samples from this genus were used to document patterns of host specificity. The comparison of these patterns with morphological variations in Anaticola revealed a general correspondence between the groups identified by DNA sequences and morphology, respectively. These results suggest that a more thorough taxonomic review of this genus is needed. In general, the groups identified on the basis of molecular data were associated with particular groups of waterfowl (e.g. dabbling ducks, sea ducks, geese) or specific biogeographic regions (e.g. North America, South America, Australia, Eurasia).

An evaluation of computer-aided disproportionality analysis for post-marketing signal detection.

To understand the value of computer-aided disproportionality analysis (DA) in relation to current pharmacovigilance signal detection methods, four products were retrospectively evaluated by applying an empirical Bayes method to Merck's post-marketing safety database. Findings were compared with the prior detection of labeled post-marketing adverse events. Disproportionality ratios (empirical Bayes geometric mean lower 95% bounds for the posterior distribution (EBGM05)) were generated for product-event pairs. Overall (1993-2004 data, EBGM05> or =2, individual terms) results of signal detection using DA compared to standard methods were sensitivity, 31.1%; specificity, 95.3%; and positive predictive value, 19.9%. Using groupings of synonymous labeled terms, sensitivity improved (40.9%). More of the adverse events detected by both methods were detected earlier using DA and grouped (versus individual) terms. With 1939-2004 data, diagnostic properties were similar to those from 1993 to 2004. DA methods using Merck's safety database demonstrate sufficient sensitivity and specificity to be considered for use as an adjunct to conventional signal detection methods.

A report of a national mutation testing service for the MEN1 gene: clinical presentations and implications for mutation testing.

INTRODUCTION: Mutation testing for the MEN1 gene is a useful method to diagnose and predict individuals who either have or will develop multiple endocrine neoplasia type 1 (MEN 1). Clinical selection criteria to identify patients who should be tested are needed, as mutation analysis is costly and time consuming. This study is a report of an Australian national mutation testing service for the MEN1 gene from referred patients with classical MEN 1 and various MEN 1-like conditions. RESULTS: All 55 MEN1 mutation positive patients had a family history of hyperparathyroidism, had hyperparathyroidism with one other MEN1 related tumour, or had hyperparathyroidism with multiglandular hyperplasia at a young age. We found 42 separate mutations and six recurring mutations from unrelated families, and evidence for a founder effect in five families with the same mutation. DISCUSSION: Our results indicate that mutations in genes other than MEN1 may cause familial isolated hyperparathyroidism and familial isolated pituitary tumours. CONCLUSIONS: We therefore suggest that routine germline MEN1 mutation testing of all cases of "classical" MEN1, familial hyperparathyroidism, and sporadic hyperparathyroidism with one other MEN1 related condition is justified by national testing services. We do not recommend routine sequencing of the promoter region between nucleotides 1234 and 1758 (Genbank accession no. U93237) as we could not detect any sequence variations within this region in any familial or sporadic cases of MEN1 related conditions lacking a MEN1 mutation. We also suggest that testing be considered for patients <30 years old with sporadic hyperparathyroidism and multigland hyperplasia.

Tau epitope display in progressive supranuclear palsy and corticobasal degeneration.

Filamentous aggregates of the protein tau are a prominent feature of Alzheimer's disease (AD), progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD). However, the extent to which the molecular structure of the tau in these aggregates is similar or differs between these diseases is unclear. We approached this question by examining these disorders with a panel of antibodies that represent different structural, conformational, and cleavage-specific tau epitopes. Although each of these antibodies reveals AD pathology, they resolved into three classes with respect to PSP and CBD: AD2 and Tau-46.1 stained the most tau pathology in all cases; Tau-1, 2, 5, and 12 exhibited variable reactivity; and Tau-66 and MN423 did not reveal any tau pathology. In addition, hippocampal neurofibrillary tangles in these cases showed a predominantly PSP/CBD-like, rather than AD-like, staining pattern. These results indicate that the patterns of the tau epitopes represented by this panel that reside in the pathological aggregates of PSP and CBD are similar to each other but distinct from that of AD.

Genetic testing in familial isolated hyperparathyroidism: unexpected results and their implications.

Familial hyperparathyroidism is not uncommon in clinical endocrine practice. It encompasses a spectrum of disorders including multiple endocrine neoplasia types 1 (MEN1) and 2A, hyperparathyroidism-jaw tumour syndrome (HPT-JT), familial hypocalciuric hypercalcaemia (FHH), and familial isolated hyperparathyroidism (FIHP). Distinguishing among the five syndromes is often difficult but has profound implications for the management of patient and family. The availability of specific genetic testing for four of the syndromes has improved diagnostic accuracy and simplified family monitoring in many cases but its current cost and limited accessibility require rationalisation of its use. No gene has yet been associated exclusively with FIHP. FIHP phenotypes have been associated with mutant MEN1 and calcium-sensing receptor (CASR) genotypes and, very recently, with mutation in the newly identified HRPT2 gene. The relative proportions of these are not yet clear. We report results of MEN1, CASR, and HRPT2 genotyping of 22 unrelated subjects with FIHP phenotypes. We found 5 (23%) with MEN1 mutations, four (18%) with CASR mutations, and none with an HRPT2 mutation. All those with mutations had multiglandular hyperparathyroidism. Of the subjects with CASR mutations, none were of the typical FHH phenotype. These findings strongly favour a recommendation for MEN1 and CASR genotyping of patients with multiglandular FIHP, irrespective of urinary calcium excretion. However, it appears that HRPT2 genotyping should be reserved for cases in which other features of the HPT-JT phenotype have occurred in the kindred. Also apparent is the need for further investigation to identify additional genes associated with FIHP.

The postmarketing safety profile of varicella vaccine.

The postmarketing safety profile of varicella vaccine was evaluated by analyzing selected adverse experience reports temporally associated with the administration of the vaccine. There were 7963 reports voluntarily submitted to Merck for an overall reporting rate of 5.0 per 10000 doses of vaccine distributed. A varicella zoster virus (VZV) identification program detected the presence of the Oka vaccine strain in three individuals with an immune deficiency - two with pneumonia and one with hepatitis - and in three instances of secondary transmission from vaccinees with vesicular lesions to susceptible household contacts. The Oka vaccine strain was present in 23 patients and wild-type VZV was present in 15 patients with herpes zoster. Vesicular rashes that occurred within 2 weeks of vaccination were more likely to contain the presence of wild-type VZV, while vesicular rashes that occurred more than 2 weeks post-vaccination were more likely to contain the Oka vaccine strain. Eleven patients were hospitalized with complications of breakthrough varicella infection.

The stress hormone, cortisol, synergizes with HIV-1 gp-120 to induce apoptosis of normal human peripheral blood mononuclear cells.

Both quantitative and qualitative defects in immune functions in patients with AIDS may result from induction of programmed cell death or apoptosis of CD4 T lymphocytes. We postulate that neurohormones may interact with gp-120 that is shed during active HIV infection and cause apoptosis of immunocompetent cells leading to immunopathogenesis of HIV infections. In this study, we investigated the synergistic effect of cortisol plus HIV gp-120 in inducing apoptosis of lymphocytes from normal subjects. Total peripheral blood mononuclear cells and isolated CD4+ T-cells were treated with cortisol or gp-120 separately and in combination and RNA and DNA were extracted. RNA was reverse transcribed and amplified with specific primers for Fas and Fas ligand and analyzed on agarose gels. DNA was analyzed by gel electrophoresis for ladder formation, the hallmark for apoptosis, and Fas antigen expression by confocal microscopy. Results demonstrate that cortisol and gp-120 induce apoptosis of lymphocytes from normal donors as demonstrated by DNA ladder formation, TUNEL staining and Fas gene expression. Concentrations of cortisol and gp-120 that did not produce apoptosis when used separately, induced significant apoptosis when used in combination. Further, gp-120 induced DNA fragmentation was significant in the CD4+ T-cell subpopulation compared to the CD47 subpopulation. This study suggests that the stress-associated neurohormone, cortisol, synergizes with HIV peptides in causing apoptosis of normal lymphocytes. The synergistic effect of cortisol and gp- 120 in inducing apoptosis of lymphocytes is consistent with a model proposing that stress-associated and circulating HIV-1 derived soluble products may cause progression of HIV infections.

Cocaine differentially modulates chemokine production by mononuclear cells from normal donors and human immunodeficiency virus type 1-infected patients.

Earlier studies have supported a significant role for cocaine in the susceptibility to and the progression of human immunodeficiency virus type 1 (HIV-1) infection. Recently, several unique HIV-1 entry coreceptors (e.g., CCR5 and CCR3) and a trio of HIV-1-specific suppressor chemokines, namely, RANTES (regulated-upon-activation T expressed and secreted), macrophage inflammatory protein 1alpha (MIP-1alpha) and MIP-1beta, were identified. Although cocaine has been linked to the immunopathogenesis of HIV-1 infection, the corresponding cellular and molecular mechanism(s) have not been well defined. We hypothesize that cocaine mediates these pathologic effects through the downregulation of HIV-1-suppressing chemokines and/or upregulating HIV-1 entry coreceptors in HIV-1-infected subjects, resulting in disease progression to AIDS. Our results show that cocaine selectively downregulates endogenous MIP-1beta secretion by normal peripheral blood mononuclear cells (PBMC), while cocaine did not affect the MIP-1beta production by PBMC from AIDS patients. Cocaine also selectively suppresses lipopolysaccharide-induced MIP-1beta production by PBMC from HIV-infected patients. Further, cocaine significantly downregulates endogenous MIP-1beta gene expression, while it upregulates HIV-1 entry coreceptor CCR5 by normal PBMC. These studies suggests a role for cocaine as a cofactor in the pathogenesis of HIV infection and support the premise that cocaine increases susceptibility to and progression of HIV-1 infection by inhibiting the synthesis of HIV-1 protective chemokines and/or upregulating the HIV-1 entry coreceptor, CCR5.

Use of losartan in the treatment of hypertensive patients with a history of cough induced by angiotensin-converting enzyme inhibitors.

The objective of this study was to determine the incidence of dry cough in hypertensive patients with a history of angiotensin-converting enzyme (ACE) inhibitor-induced cough after treatment with losartan (an angiotensin II-receptor antagonist), lisinopril (an ACE inhibitor), or placebo. One hundred patients from 16 outpatient treatment centers in the United States were included in this double-masked, randomized, parallel-group, active- and placebo-controlled study, with stratification according to sex. After a challenge phase with lisinopril and a placebo washout phase, patients were randomly allocated to receive losartan 50 mg once daily, lisinopril 20 mg once daily, or placebo for a maximum of 8 weeks. The primary efficacy end point of the study was the presence or absence of dry cough during the double-masked period, as rated by the patient at each visit using a validated symptom assessment questionnaire. A secondary end point was the frequency of dry cough, as measured at each visit using a visual analogue scale (VAS). The incidence of dry cough was significantly higher in the lisinopril group than in the losartan and placebo groups (87.5% vs 36.7% and 31.4%, respectively) at the end of the double-masked treatment period; there was no statistically significant difference between the losartan and placebo groups. Mean VAS scores showed that patients treated with lisinopril rated themselves as having a significantly higher frequency of cough than did patients treated with losartan or placebo (4.0 vs 1.2 and 1.5, respectively). Again, the difference between the losartan and placebo groups was not statistically significant. All treatments were otherwise well tolerated, and no serious clinical or laboratory adverse events were reported during the double-masked phase of the study. These results demonstrate that the incidence, severity, and frequency of dry cough in patients with a history of ACE inhibitor-induced dry cough are significantly lower in those treated with losartan than in those treated with lisinopril and are similar to the incidence, severity, and frequency of dry cough in those receiving placebo.

Immunoregulatory effects of morphine on human lymphocytes.

It is now well established that parenteral drug abuse is a significant risk factor for contracting human immunodeficiency virus type 1 (HIV-1) infection and subsequently developing AIDS. Earlier studies have shown that morphine can modulate various immune responses and therefore support the premise that morphine is a cofactor in susceptibility to and progression of HIV infection. Dysregulation of interferon (IFN) production, nonspecific apoptosis of T cells, and the immune response to soluble HIV gene products have been associated with potential mechanisms of pathogenesis in HIV disease. The present study was undertaken to examine the immunomodulatory role of morphine on HIV protein-induced lymphocyte proliferative responses, Sendai and Newcastle disease virus-induced alpha IFN (IFN-alpha) and IFN-beta production by lymphocytes and fibroblast cells, respectively, and induction of apoptosis of normal lymphocytes in vitro. Our results demonstrate that HIV protein-induced human lymphocyte proliferative responses were significantly inhibited by morphine in a dose-dependent manner. Furthermore, morphine significantly inhibited both IFN-alpha and IFN-beta production by normal lymphocytes and fibroblasts but induced apoptosis of normal lymphocytes. Inhibition of IFN-alpha production by morphine could be reversed by the opiate receptor antagonist naloxone. This suggests that the immunomodulatory effects of morphine are mediated through the opioid receptor. These studies support a role of morphine as a cofactor in the pathogenesis of HIV infection and describe some of the possible pathologic mechanisms which underlie the immunoregulatory effects of morphine.

The effects of lesions to thalamic lateral internal medullary lamina and posterior nuclei on learning, memory and habituation in the rat.

The behavioral effects of radiofrequency lesions to the lateral internal medullary lamina region (IML) or the posterior region (Po: containing the parafascicular and posterior nuclei) of the thalamus were compared to sham operated controls. Subjects were pre-operatively trained and then tested for post-operative retention of a NMTP task. Whereas the Po-lesion group was impaired only on long delays (60, 90 s), the IML-lesion group was impaired on retention and re-acquisition and demonstrated lower performance at all delays (5-90 s) of the NMTP task. Post-operative training and testing was conducted on three additional tasks: Morris water maze, acoustic startle, and passive avoidance. The IML-lesion group was impaired in finding a hidden and visual platform in the Morris water maze, demonstrated a blunted response but normal habituation to an acoustic startle stimulus, and showed normal retention of a passive avoidance task. On those three tasks, the performance of the Po-lesion group was similar to controls. In the IML-lesion group, neuronal loss resulting from axotomy and/or transneuronal degeneration was observed within nuclei of the midline and anterior thalamus and the mammillary body. These results suggest that lesions to the IML region disrupt a range of cognitive functions and produce pathological destruction in distant brain regions; whereas damage to the posterior thalamus causes spatial delay-sensitive deficits.

Organ donation and transplantation.

Organ donation and transplantation are highly controversial and emotive areas of nursing ( 1 ). Nonetheless, sudden death is a continual issue in the A&E department, thus creating a potential source of donors for transplantation purposes ( 2 ). This article will consider what organs would be suitable for retrieval in A&E, what appears to be restricting this process, and means of improving the rate of retrieval.

Differential effects of human immunodeficiency virus type 1 envelope protein gp120 on interferon production by mononuclear cells from adults and neonates.

While considerable progress in examining the course of human immunodeficiency virus (HIV) infection in adults has been made, a better understanding of the natural history of perinatal HIV infection remains to be obtained. Dysregulation of the production and functions of various cytokines, especially the interferons (IFNs), during HIV infections has been reported. Using an in vitro model system, we examined the effects of the HIV type 1 envelope protein, gp120 (10, 50, and 100 ng/ml), on gamma IFN (IFN-gamma) and IFN-alpha production by lymphocytes from neonates and adults and also examined the potential regulatory effects of gp120 on phorbol 12-myristate acetate (PMA)- and Sendai virus-induced IFN-gamma and IFN-alpha production by lymphocytes. PMA at a concentration of 50 ng/ml plus 50 ng of calcium ionophore A23187 per ml was used to induce IFN-gamma, while 150 hemagglutinating units of Sendai virus was used to induce IFN-alpha production. The antiviral activity of both IFN-alpha and IFN-gamma in leukocyte culture supernatants was assayed on BG-9 cells by a dye uptake technique using vesicular stomatitis virus as a challenge virus. Placental cord blood leukocyte (CBL) samples from healthy, term infants and adult peripheral blood leukocytes (APBL) produced no IFN in response to gp120. However, CBL produced significantly decreased levels of IFN-gamma compared with APBL in response to PMA plus ionophore. gp120 significantly suppressed both Sendai virus-induced IFN-alpha and PMA-induced IFN-gamma production by both CBL and APBL in a dose-dependent manner. However, gp120-induced suppression of IFN-alpha and IFN-gamma was significantly greater with CBL than with APBL. Treatment of CBL and APBL with gp120 did not induce any phenotypic alteration of the CD45 RO+ subset. Increased suppression of IFN-alpha and IFN-gamma production by gp120 in neonates may partially explain their apparent increased susceptibility to the clinical progression of HIV infections compared with that of adults.

Inhibition of interleukin 1-induced biosynthesis of stromelysin by the calcium antagonist TMB-8 (8-(N, N-diethylamino)octyl-3,4,5-trimethoxybenzoate HCl).

This study was done to identify agents that can inhibit interleukin 1 (IL1)-induced stromelysin biosynthesis and to gain insight into the mechanism of IL1 action. For this purpose, various agents known to modulate calcium-dependent signal transduction pathway were evaluated in rabbit synovial fibroblast (RSF) cultures. Only the conditioned medium from RSF treated with the intracellular calcium antagonist TMB-8 (8-(N,N-diethylamino)-octyl 3,4,5-trimethoxybenzoate hydrochloride) had significantly lower proteoglycan-degrading metalloproteinase activity than controls. Biosynthetic labeling, immunoprecipitation and immunohistochemical studies, using a polyclonal antibody against rabbit stromelysin, demonstrated that TMB-8 inhibited synthesis stromelysin, the proteoglycan-degrading matrix metalloproteinase. Further evaluation of the TMB-8 effect revealed that the compound had no effect on secretion and that it was not acting by preventing activation of the proenzyme or by inhibiting the enzyme activity. These results suggest that TMB-8 may be inhibiting stromelysin synthesis by limiting intracellular calcium levels.

Selective inhibition by alcohol and cortisol of natural killer cell activity of lymphocytes from cord blood.

1. The immunosuppressive effects of drugs such as alcohol or hormones such as cortisol may be age-related. To test this hypothesis, the authors investigated the in vitro effects of ethanol (EtOH) and cortisol on Natural Killer (NK) cell activity of lymphocytes from normal cord blood in comparison with that of lymphocytes from normal adult peripheral blood. 2. K562, an erythroleukemia cell line, was used as a target in a 4 hr 51Cr release assay. 3. Ethanol at 0.3% (V/V) and cortisol at 0.05, 0.1 and 0.2 microgram/ml concentrations, added directly to a mixture of effector and target cells significantly suppressed the NK activity of cord blood lymphocytes in a dose dependent fashion, whereas similar concentrations of either EtOH or cortisol did not manifest significant immunoregulatory effects on NK cell activity of normal adult lymphocytes. 4. Pre-treatment of the target with either EtOH or cortisol for 4 hours did not affect cytotoxicity. Inhibition of cytotoxicity was also not due to direct toxicity of effector cells because lymphocytes treated with either EtOH or cortisol showed normal 51Cr release and their viability was comparable to that of untreated control cells. 5. This suggests a selective inhibitory effect of EtOH and cortisol on NK activity of neonatal lymphocytes that may be of clinical significance.