Inhibition of the Mixed Lymphocyte Culture Response by Antibody Following Successful Human Renal Transplantation

Immunoglobulin G, appearing after several months in the serum of a recipient of a successful kidney transplant from a closely matched sibling donor, was demonstrated to progressively inhibit unidirectional mixed lymphocyte cultures when donor lymphocytes were used either in responding or stimulating cell populations. The active recipient IgG had no effect in cultures in which donor cells were not used, nor did IgG obtained from other individuals show nonspecific inhibitory effects on cultures containing donor cells. It is suggested that the MLC inhibitory immunoglobulin may serve an immunoregulatory function after renal transplantation.     

Phenotype and functional analysis of human monocyte-derived dendritic cells loaded with biodegradable poly(lactide-co-glycolide) microspheres for immunotherapy

Dendritic cells (DC) are increasingly explored as cellular vaccines for tumor immunotherapy. In most reported DC-based cancer vaccine trials, DC have been pulsed with soluble tumor antigen-derived peptide ligands of MHC molecules. Considering that the half-life of peptide/MHC complexes on the cell surface is relatively short and that soluble exogenous protein antigens cannot be efficiently processed via the MHC class I-processing pathway, the current vaccination procedure is not optimal for the induction of strong T cell responses aiming at tumor rejection. Recently, we have shown that antigen presentation can be prolonged when synthetic peptides were encapsulated in biodegradable poly(D,L-lactide-co-glycolide) (PLGA) microspheres (MS) for uptake by DC. In the present study, we investigated the phenotypic and functional consequences of MS uptake by human monocyte-derived dendritic cells (MoDC) in vitro. We found that immature MoDC that were prepared in serum free media suitable for clinical application were able to phagocytose high numbers of MS, while matured MoDC showed a reduced capacity for phagocytosis of MS. The ingestion of MS did not change the cell surface expression of CD80, CD83, CD86 and HLA-DR of immature and mature DC, suggesting that MS uptake did not induce DC maturation but that maturation by cytokines or LPS was unaltered in the presence of MS. Furthermore, MS-loaded mature MoDC expressed normal levels of the chemokine receptor CCR7 and migrated as efficiently towards CCL19 or CCL21 as unloaded MoDC. DC viability and the secretion of TNF-alpha and IL-12 was not significantly changed by MS loading. Taken together, our data indicate that PLGA-MS loading has no negative effects on the pivotal properties of MoDC in vitro. It should therefore be feasible to further develop this antigen loading strategy for clinical use in immunotherapy against viral infections and tumors.     

APO-1(CD95)-dependent and -independent antigen receptor-induced apoptosis in human T and B cell lines

Certain B and T cell lines respond to activation signals, e.g.through the antigen receptor, by undergoing apoptotlc cell death.In T cells it has been recently shown that TCR-mediated apoptosisinvolves APO-1/Fas (CD95) receptor-ligand interaction. To investigatewhether the TCR-CD3 complex can trigger alternative apoptosispathways we generated subclones of the T cell line Jurkat whichwere completely resistant towards APO-1-mediated apoptosis.These Jurkat^R cells differed phenotypically from sensitive parentalJurkat^S cells only by the lack of APO-1 protein expression.Although Jurkat^R cells responded normally to anti-CD3 stimulationby expression of APO-1 ligand they failed to undergo anti-CD3-inducedapoptosis. Thus, in Jurkat cells APO-1 -mediated apoptosis wasthe main, and might be the only, mechanism for anti-CD3-inducedcell death. However, BL-60 B cells, highly sensitive to anti-IgM-inducedapoptosis, did not use the APO-1 receptor-ligand system becausethey failed to express APO-1 ligand mRNA. Taken together, ourresults suggest that malignant T and B cell lines may use APO-1receptor-ligand-dependent and -independent antigen receptor-inducedapoptosis pathways respectively. Similarly, differential pathwaysmay be used by T and B cell subsets.     

Factors associated with the use of psychiatric consultations in short-term general hospitals

A significant number of patients in general hospitals suffer from psychiatric distress or illness, but not all receive psychiatric consultation. This study examined several potential predictors of such consultation. These included patient characteristics (age, sex, race, insurance, disease stage, and number of medical diagnoses), characteristics of hospital stay (number of procedures, other consultations, length of stay, discharge destination), hospital characteristics (size, percent occupancy, teaching status, presence of a psychiatric unit, type of control), and community characteristics (region, urban/rural setting). Data were derived from a national sample of 327 hospitals. Parallel analyses using stepwise logistic regression were carried out across four samples: patients determined at discharge to have been hospitalized for diabetes, hip fracture, chronic obstructive pulmonary disease, and coronary artery bypass surgery. Results show a wide variation in the use of psychiatric consultations across different subgroups. Longer lengths of stay, urban setting. Northeast region, younger patient age, and other consultations were the most consistent predictors of the probability of psychiatric consultation. These variations may reflect differences in the need for consultation, differential recognition of these needs by providers, or differential availability of psychiatric consultation services. Moreover, they may have implications for equity and/or quality of hospital care.     

Separation of mycobacterial soluble antigens by isoelectric focusing

Ion-exchange chromatography and gel filtration have been reported to yield partial separation of mycobacterial antigens. These procedures were used in combination with isoelectric focusing in an attempt to purify antigens of Mycobacterium tuberculosis strain H37Ra. The fractionating action of isoelectric focusing is dependent upon differences in the isoelectric points of the proteins to be separated. Culture filtrate of M. tuberculosis H37Ra was chromatographed on Sephadex G-200. This resulted in two widely separated peaks. The first peak, presumably containing high-molecular-weight substances, was then fractionated on a diethylaminoethyl Sephadex anion-exchange column. Three peaks were collected, and each was subjected to isoelectric focusing. Each peak was further separated into two or more fractions. The serological reactivity of each fraction was determined by immunodiffusion and immunoelectrophoresis. Sensitized guinea pigs were also skin-tested with the fractions. Two of the fractions contained only a single precipitinogen. One fraction contained two precipitinogens. A fourth fraction contained three precipitinogens and was also the only fraction to display sensitin activity. Four of the fractions were inactive either as precipitinogens or sensitins. The results suggest that the methods described are useful for the separation of mycobacterial antigens.     

Tobacco withdrawal in women and menstrual cycle phase

Because negative mood is a characteristic of both tobacco withdrawal and menstrual discomfort, withdrawal may vary by menstrual cycle phase. Tobacco withdrawal, mood, and menstrual discomfort were assessed in premenopausal women who quit smoking during either the follicular (Days 1-14 postmenstrual onset; n = 41) or luteal (Day 15 or longer postmenstrual onset; n = 37) phase of the menstrual cycle and maintained biochemically verified smoking abstinence during the postquit week. Women quitting during the luteal phase reported significantly greater increases in tobacco withdrawal and self-reported depressive symptoms than women quitting during the follicular phase. These results indicate that selecting a quit-smoking day early in the follicular phase may attenuate withdrawal and negative affect in premenopausal female smokers.