Enolase 1 of Candida albicans binds human CD4+ T cells and modulates naïve and memory responses

To obtain a better understanding of the biology behind life-threatening fungal infections caused by Candida albicans, we recently conducted an in silico screening for fungal and host protein interaction partners. We report here that the extracellular domain of human CD4 binds to the moonlighting protein enolase 1 (Eno1) of C. albicans as predicted bioinformatically. By using different anti-CD4 monoclonal antibodies, we determined that C. albicans Eno1 (CaEno1) primarily binds to the extracellular domain 3 of CD4. Functionally, we observed that CaEno1 binding to CD4 activated lymphocyte-specific protein tyrosine kinase (LCK), which was also the case for anti-CD4 monoclonal antibodies tested in parallel. CaEno1 binding to naïve human CD4⁺ T cells skewed cytokine secretion toward a Th2 profile indicative of poor fungal control. Moreover, CaEno1 inhibited human memory CD4⁺ T-cell recall responses. Therapeutically, CD4⁺ T cells transduced with a p41/Crf1-specific T-cell receptor developed for adoptive T-cell therapy were not inhibited by CaEno1 in vitro. Together, the interaction of human CD4⁺ T cells with CaEno1 modulated host CD4⁺ T-cell responses in favor of the fungus. Thus, CaEno1 mediates not only immune evasion through its interference with complement regulators but also through the direct modulation of CD4⁺ T-cell responses.     

Dementia praecox and manic-depressive insanity in 1908: A Grade of Membership analysis of the Kraepelinian dichotomy

Grade of Membership (GoM) analysis, a multivariate classification technique based on fuzzy-set mathematics, was applied to the demographic, history, and mental-state data on 53 dementia praecox cases and 134 manic-depressive insanity cases admitted to Kraepelin's University Psychiatric Clinic in Munich in 1908. The original data recorded by Kraepelin and his collaborators on specialZählkarten (counting cards) were rated and coded in terms of the Present State Examination (PSE) Syndrome Check List. The statistical analysis resulted in a high degree of replication of Kraepelin's clinical entities. However, the dichotomy of dementia praecox and manic-depressive insanity was not fully supported. The catatonic syndrome tended to occupy an intermediate position between the two major psychoses. The possibility is discussed that catatonia in Kraepelin's time shared certain clinical features with the later diagnostic groupings of schizoaffective disorder, cycloid psychoses, and other atypical forms of psychotic illnesses.     

Gender differences in HIV risk behaviors in an adult emergency department in New York City

Background The human immunodeficiency virus (HIV) epidemic in the US increasingly involved urban heterosexual adults, particularly women, belonging to ethnic minority groups. An understanding of gender-based differences in HIV risk behaviors within these groups would be of value in the ongoing struggle to limit HIV transmission in metropolitan centers. Methods This was a prospective study of demographic and historical characteristics and HIV risk behaviors. The study utilized a structured interview format, which was administered to all patients treated by participating emergency department physicians. Results On univariate analysis of data obtained from 1,460 patients who had neither a known HIV infection nor a chief complaint or final emergency department diagnosis associated with HIV risk behaviors, men were more likely to be older, homeless, to have ever injected drugs, used crack, engaged in same-gender sex, paid for sex, been incarcerated, or had syphilis or gonorrhea. Women were more likely to report prior chlamydia infection or to report that their sole sex partners had other partners within the past year. On multivariate analysis, variables independently associated with male gender included homelessness, injection drug use, crack use, any prior sexually transmitted disease (in subjects 35 years of age or older), and sex with prostitutes. In a separate analysis of patients admitting to drug use, the male predominance of other risk behaviors was not observed; the only significant differences between genders were a higher rate of prostitution among women and a higher rate of sexual contact with a prostitute among men. Conclusions In patients visiting an inner-city emergency department in the Bronx, HIV risk behaviors are generally more common in men, but rates of risk behaviors among male and female drug users are comparable. This work was supported in part by a collaborative agreement with the Centers for Disease Control and Prevention (U64/CCU200714). Drs. Shuter, Alpert, and DeShaw were supported in part by a training grant (5-T32-AI070183) from the National Institute of Allergy and Infectious Diseases. This study was presented in part at the 32nd Annual Meeting of the Infectious Diseases Society of America, October 1994, Orlando, Florida.     

Cost of smoking to the Medicare program, 1993

Medicare expenditures attributable to smoking in 1993 were estimated using a multivariate model that related expenditures to smoking history, health status, and the propensity to have had a smoking-related disease, controlling for sociodemographics, economic variables, and other risk factors. Smoking-attributable Medicare expenditures are presented separately for each State and by type of expenditure. Nationally, smoking accounted for 9.4 percent of Medicare expenditures--$14.2 billion, with considerable variation among States. Smoking accounted for 11.4 percent of Medicare expenditures for hospital care, 11.3 percent of nursing home care, 5.9 percent of home health care, and 5.6 percent of ambulatory care.     

Caffeine Pretreatment Enhances Clinical Efficacy and Reduces Cognitive Effects of Electroconvulsive Therapy

In an open clinical trial, depressed patients received age-dosed, brief-pulse electroconvulsive therapy (ECT) either with or without 500 mg i.v. caffeine sodium benzoate before each treatment. Caffeine-pretreated patients required fewer ECT treatments, and after three to four treatments, their Hamilton Depression Scale (HDS) scores were significantly lower. At the end of the ECT course, both groups reached the same reduction in HDS scores. Of five memory tests, one showed better performance at the end of the ECT course for the caffeine-pretreated compared with the non-caffeine-pretreated patients. The results argue that caffeine-modified ECT differs from unmodified ECT in speed of response and the effects on cognitive tests.     

Reversible Dementia and Affective Disorder: The Rip Van Winkle Syndrome

The diagnostic separation of the reversible dementia of an affective disorder from the dementia secondary to structural brain pathology remains a clinical challenge. A 58-year-old woman had been diagnosed as having Alzheimer's dementia for 9 years before antidepressant treatment with electroconvulsive therapy (ECT) resolved the dementia syndrome. The patient has functioned well for 8 years on maintenance treatment with lithium, with ECT given every 7-8 weeks. By the summer of 1993, she had undergone 132 ECT. Until specific and reliable pre-morbid tests for the diagnosis of irreversible dementias of the Alzheimer's and multiinfarct types are developed, antidepressant treatment trials are encouraged in elderly patients with a dementia syndrome. Extensive maintenance ECT schedules are safe.     

Autoradiography of 14C-choline uptake in endplates and skeletal muscle of mice

Summary The uptake of ¹⁴C-choline into the axonal part of the motor endplate and muscle of mouse diaphragms was investigated by autoradiography. With i. v. doses of 0.1 g/g choline chloride, the uptake into the nerve endings is fast (<2 min) and into muscle slower (>2 min). With higher doses (1.0 g/g) the uptake into muscle tissue is accelerated.The radioactivity in the endplates decreases with a halflife time of 20 min and remains constant in the muscle fibres over 60 min. Denervation by cutting the phrenic nerve reduces the uptake into endplates by 40% within 14 h, but probably induces uptake into regenerating Schwann cells during 30 days. Some compounds with choline-like structure (hemicholinium-3, decamethylen-dicholine, triethyl-choline) reduce the high-affinity uptake of choline into the nerve endings with sublethal doses, whereas tetraethylammonium and N-hydroxyethyl-4-(1-naphthylvinyl)-pyridinium, an inhibitor of cholinacetyltransferase, are less active. Half lethal doses of cocaine, imipramine and reserpine have no significant action on uptake of choline into the endplates. Chlorpromazine slightly diminishes the uptake into endplates. Chlorpromazine and imipramine reduce uptake into the muscle fibres.     

Rabbit immunoglobulin kappa genes: structure of a germline b4 allotype J-C locus and evidence for several b4-related sequences in the rabbit genome.

To investigate the genetic mechanism by which certain rabbits can express immunoglobulins unexpected on the basis of their pedigree (i.e., "latent" allotypes), we have begun a study of the rabbit immunoglobulin kappa gene locus. Here we report the structure of a germline genomic clone that encodes the b4 allotype of rabbit kappa immunoglobulin and corresponds to the kappa gene expressed by the rabbit-mouse hybridoma 12F2. The nucleotide sequences of the joining (J) and constant (C) regions reveal structures generally similar to the homologous mouse and human loci, although only one of the five J-like sequences of this rabbit gene is apparently expressed. Southern blotting analysis of DNA from several rabbit allotypic strains by using probes derived from the cloned b4 gene demonstrates that, in contrast to mouse and human, rabbits possess multiple kappa-related sequences. Rabbits of the nominal b4, b5, b6, and b9 allotypes each contain at least two b4-related sequences that are associated with their own J regions and that are highly homologous to the cloned b4 gene in both coding and flanking regions.