Metabolites of alveolarEchinococcus as determined by [31P]- and [1H]-nuclear magnetic resonance spectroscopy

[³¹P]-Nuclear magnetic resonance (NMR) in vivo spectra ofEchinococcus multilocularis cysts growing subcutaneously inMeriones unguiculatus showed prominent signals due to phosphomonoesters (PME), phosphodiesters (PDE), inorganic phosphate (Pi) and the , and phosphate groups of adenosine triphosphate (ATP). The internal pH of the parasite cysts was 6.7–6.8. The³¹P spectra of extracts of these subcutaneous cysts showed peaks identified as glucose-6-phosphate (Glu-6-P), glycerol-3-phosphate (Gly-3-P), phosphorylethanolamine (PE), adenosine-5-monophosphate (5-AMP), nicotinamide adenine dinucleotide phosphate (NADP), phosphorylcholine (PC), Pi, glycerolphosphorylethanolamine (GPE), glycerolphosphorylcholine (GPC), phosphoenolpyruvate (PEP), adenosine diphosphate (ADP), ATP and diphosphodiesters (DPDE). These metabolites were also detected at comparable concentrations in the extracts of intraperitoneally grown cysts. In addition, significantly more phosphocreatine (PCr), probably of host origin, was detected in the subcutaneous cysts than in the intraperitoneal cysts. [¹H]-NMR spectra of cyst extracts revealed that parasites grown in the abdominal cavity contained significantly less glucose but significantly more succinate, acetate, alanine and -hydroxybutyrate. Glycogen, creatine, glycine, taurine, betaine, cholines and lactate were present at similar concentrations in cyst material from both locations.     

Antigen-specific desensitization of patients allergic to penicillin

Three penicillin-allergic patients with life-endangering infections requiring β-lactam antibiotic therapy were desensitized by means of increasing oral then parenteral doses and were treated with full doses of β-lactam agents. Malignant otitis externa caused by Pseudomonas aeruginosa, osteomyelitis caused by Staphylococcus aureus, and bacterial endocarditis caused by an enterococcus were treated with carbenicillin, nafcillin, and benzylpenicillin G, respectively. No acute allergic reactions occurred during desensitization or within 1 wk of the onset of therapy. Immediate wheal and flare skin-test reactions to β-lactam determinants diminished or became negative after the desensitization procedure in each patient. Wheal and flare responses provoked by histamine, compound 48/80, and environmental antigens were not affected by the desensitization procedure or continued β-lactam drug therapy. Mild urticaria appeared after 15 days of penicillin therapy in one patient and after 23 days of carbenicillin therapy in another patient. Skin-test reactions to penicillin reagents had reverted to positive at the time of the urticarial reactions. One patient developed a severe immune hemolytic anemia after 10 days of therapy with nafcillin. The results of this study indicate that acute clinical desensitization of these three penicillin-allergic patients was associated with antigen-specific desensitization of tissue mast cells.     

Relationship quality moderates the effect of social support given by close friends on cardiovascular reactivity in women

We examined the role of the type of support provided, gender of support provider, and relationship quality in predicting how social support might influence cardiovascular reactivity during acute stress in women. A group of 88 women received either emotional, instrumental, or no support from a close female or male friend while performing a series of speech tasks. Results suggest that the effectiveness of social support for women depended primarily on the quality of the friendship (i.e., purely positive, or ambivalent). More specifically, women who interacted with a female, ambivalent friend had the largest changes in diastolic blood pressure, total peripheral resistance (TPR), and pre-ejection period compared to the other conditions. Furthermore, receiving emotional support from a purely positive friend was related to lower increases in cardiac output (CO) compared to a no-support condition. In contrast, receiving emotional support from an ambivalent friend was related to larger increases in CO and only small changes in TPR when compared to individuals in the no-support condition. These data are discussed in light of the psychosocial processes underlying social support effects in women, and the importance of a more comprehensive view of how close relationships influence cardiovascular function. This research was generously supported by Grant1 R01 MH58690-01 from the National Institute of Mental Health awarded to Bert N. Uchino.     

Identification of vaccine candidate peptides in the NcSRS2 surface protein of Neospora caninum by using CD4+ cytotoxic T lymphocytes and gamma interferon-secreting T lymphocytes of infected holstein cattle

Previously, our laboratory showed that Holstein cattle experimentally infected with Neospora caninum develop parasite-specific CD4+ cytotoxic T lymphocytes (CTL) that lyse infected, autologous target cells through a perforin-granzyme pathway. To identify specific parasite antigens inducing bovine CTL and helper T-lymphocyte responses for vaccine development against bovine neosporosis, the tachyzoite major surface proteins NcSAG1 and NcSRS2 were targeted. In whole tachyzoite antigen-expanded bovine T-lymphocyte lines, recombinant NcSRS2 induced potent memory CD4+- and CD8+-T-lymphocyte activation, as indicated by proliferation and gamma interferon (IFN-gamma) secretion, while recombinant NcSAG1 induced a minimal memory response. Subsequently, T-lymphocyte epitope-bearing peptides of NcSRS2 were mapped by using overlapping peptides covering the entire NcSRS2 sequence. Four experimentally infected cattle with six different major histocompatibility complex (MHC) class II haplotypes were the source of immune cells used to identify NcSRS2 peptides presented by Holstein MHC haplotypes. NcSRS2 peptides were mapped by using IFN-gamma secretion by rNcSRS2-stimulated, short-term T-lymphocyte cell lines, IFN-gamma enzyme-linked immunospot (ELISPOT) assay with peripheral blood mononuclear cells, and 51Cr release cytotoxicity assay of rNcSRS2-stimulated effector cells. Four N. caninum-infected Holstein cattle developed NcSRS2 peptide-specific T lymphocytes detected ex vivo in peripheral blood by IFN-gamma ELISPOT and in vitro by measuring T-lymphocyte IFN-gamma production and cytotoxicity. An immunodominant region of NcSRS2 spanning amino acids 133 to 155 was recognized by CD4+ T lymphocytes from the four cattle. These findings support investigation of subunit N. caninum vaccines incorporating NcSRS2 gene sequences or peptides for induction of NcSRS2 peptide-specific CTL and IFN-gamma-secreting T lymphocytes in cattle with varied MHC genotypes.     

Trends in HIV prevalence among public sexually transmitted disease clinic attendees in the Western region of the United States (1989-1999)

OBJECTIVES: Using data from anonymous unlinked testing of routinely collected sera, trends in HIV are compared among sexually transmitted disease patients in 4 Western urban centers. METHODS: Between 1989 and 1999, remnant sera obtained for routine syphilis testing from 256,819 patient visits to Denver, Los Angeles, San Francisco, and Seattle clinics were tested for HIV antibodies in an unlinked survey. HIV antibody test results were linked to anonymous demographic and risk information abstracted from the medical record. RESULTS: Overall cumulative HIV seroprevalences among women and among men who had sex exclusively with women were < or = 2%, declined over time, and did not exceed 8% among those who injected drugs. In contrast, cumulative HIV seroprevalences among men who have sex with men ranged from 13% in Seattle to 30% in San Francisco and declined a mean of 2.1% (95% CI, 1.6, 2.6) to 2.8% (CI 2.6, 3.1) per year, after adjustment. CONCLUSIONS: HIV infection declined over time across counties. Relative levels of HIV differed little by demographic and behavioral risk group despite differences in the severity of each county's epidemic. Because of the unique contribution of unlinked serosurveillance studies in monitoring these trends, their reinstitution in high-risk settings should be considered.     

Fornix transection impairs conditional visuomotor learning in tasks involving nonspatially differentiated responses.

Rhesus monkeys learned a series of conditional visuomotor associations involving two-dimensional "objects" that instructed one of three responses: tapping a touch screen, steady contact with the screen for a brief period, or steady contact for a longer period. Relative to controls, fornix-transected monkeys were impaired in the acquisition of new associations and in the retention of preoperatively learned ones. These findings challenge the view that the hippocampal system participates in associative learning only when spatial information is relevant to either the stimulus or the response.