Type C retrovirus released from porcine primary peripheral blood mononuclear cells infects human cells

As part of the evaluation of porcine cells, tissues, and organs intended for transplantation into humans, we investigated the conditions required to induce expression and release of porcine endogenous retrovirus (PoEV) from primary cells. Pigs contain endogenous retroviral sequences encoding infectious retrovirus, yet little is known about the conditions required to activate the expression and release of PoEV from primary cells. We show here that mitogenic activation of peripheral blood mononuclear cells (PBMC) isolated from the National Institutes of Health (NIH) miniature pig and the Yucatan pig resulted in the activation and release of an infectious type C retrovirus. Coculture of activated porcine PBMC with pig or human cell lines resulted in the transfer and expression of PoEV-specific sequences and the establishment of a productive infection. Sequence comparison of portions of the PoEV pol gene expressed in pig cell lines productively infected with virus derived from NIH miniature pig and Yucatan pig PBMC revealed marked similarity, suggesting that one or a few loci may be capable of being activated to yield an infectious virus. These findings demonstrate that the presence of endogenous viruses in source animals needs to be carefully considered when the infectious disease potential of xenotransplantation is being assessed.     

Zinc deficiency increases hypothalamic neuropeptide Y and neuropeptide Y mRNA levels and does not block neuropeptide Y-induced feeding in rats

Zinc deficiency reduces intake and produces an unusual approximately 3.5-d cycle of intake in rats. The mechanism underlying the anorexia and cycling has not yet been defined; current hypotheses suggest that alterations in amino acid metabolism and neurotransmitter concentrations may be a part of this anorexia. Recent reports indicate that appetite-stimulating neuropeptide Y (NPY) may be elevated during zinc deficiency. This suggests that a resistance to NPY may exist during zinc deficiency because NPY levels are high, yet appetite is low. The purpose of this study was to measure NPY peptide and mRNA concentrations during zinc deficiency in specific nuclei of the hypothalamus in which peptide and mRNA for NPY are known to be associated with appetite, and also to determine whether zinc-deficient rats are responsive to central infusions of NPY. Both NPY peptide levels in the paraventricular nucleus and NPY mRNA levels in the arcuate nucleus were higher (P < 0.05) in zinc-deficient rats than in zinc-adequate rats. When rats were administered exogenous NPY to the paraventricular nucleus, both zinc-deficient and zinc-adequate rats responded similarly by increasing food intake. These results suggest that NPY is elevated during zinc deficiency in an attempt to restore normal food intake levels, rather than being reduced and thereby contributing to the anorexia associated with zinc deficiency. During zinc deficiency, NPY receptors are able to bind NPY and initiate an orexigenic response.     

Activity Counseling Trial (ACT): rationale, design, and methods. Activity Counseling Trial Research Group

The Activity Counseling Trial (ACT) is a multicenter, randomized controlled trial to evaluate the effectiveness of interventions to promote physical activity in the primary health care setting. ACT has recruited, evaluated, and randomized 874 men and women 35-75 yr of age who are patients of primary care physicians. Participants were assigned to one of three educational interventions that differ in amount of interpersonal contact and resources required: standard care control, staff-assisted intervention, or staff-counseling intervention. The study is designed to provide 90% power in both men and women to detect a 1.1 kcal.kg-1.day-1 difference in total daily energy expenditure between any two treatment groups, and over 90% power to detect a 7% increase in maximal oxygen uptake, the two primary outcomes. Primary analyses will compare study groups on mean outcome measures at 24 months post-randomization, be adjusted for the baseline value of the outcome measure and for multiple comparisons, and be conducted separately for men and women. Secondary outcomes include comparisons between interventions at 24 months of factors related to cardiovascular disease (blood lipids/lipoproteins, blood pressure, body composition, plasma insulin, fibrinogen, dietary intake, smoking, heart rate variability), psychosocial effect, and cost-effectiveness, and at 6 months for primary outcome measures. ACT is the first large-scale behavioral intervention study of physical activity counseling in a clinical setting, includes a generalizable sample of adult men and women and of clinical setting, and examines long-term (24 months) effects. ACT has the potential to make substantial contributions to the understanding of how to promote physical activity in the primary health care setting.     

Experience with oral methylprednisolone in the treatment of refractory hyperemesis gravidarum

OBJECTIVE: Our purpose was to describe the effect of oral methylprednisolone on the course of refractory hyperemesis gravidarum. STUDY DESIGN: Patients with intractable hyperemesis gravidarum were candidates for oral methylprednisolone. Forty-eight milligrams per day was given for 3 days followed by a tapering dose over 2 weeks. If vomiting recurred after 2 weeks of therapy or during tapering, the medication was restarted or extended but not longer than 1 month total. RESULTS: Seventeen of 18 patients (94%) were free of vomiting and were able to tolerate a regular diet within 3 days. Seven did not have further symptoms during their pregnancies. Nine vomited during or after tapering, but 7 of these responded to extension or reinstitution of therapy. Four of 6 patients on total parenteral nutrition at the start of therapy had a complete response within 3 days. CONCLUSIONS: A short course of oral methylprednisolone appears to be a reasonable therapeutic alternative for intractable hyperemesis.     

Mycobacterium avium complex augments macrophage HIV-1 production and increases CCR5 expression

Infection with HIV-1 results in pronounced immune suppression and susceptibility to opportunistic infections (OI). Reciprocally, OI augment HIV-1 replication. As we have shown for Mycobacterium avium complex (MAC) and Pneumocystis carinii, macrophages infected with opportunistic pathogens and within lymphoid tissues containing OI, exhibit striking levels of viral replication. To explore potential underlying mechanisms for increased HIV-1 replication associated with coinfection, blood monocytes were exposed to MAC antigens (MAg) or viable MAC and their levels of tumor necrosis factor alpha (TNFalpha) and HIV-1 coreceptors monitored. MAC enhanced TNFalpha production in vitro, consistent with its expression in coinfected lymph nodes. Using a polyclonal antibody to the CCR5 coreceptor that mediates viral entry of macrophage tropic HIV-1, a subset of unstimulated monocytes was shown to be CCR5-positive by fluorescence-activated cell sorter analysis. After stimulation with MAg or infection with MAC, CCR5 expression was increased at both the mRNA level and on the cell surface. Up-regulation of CCR5 by MAC was not paralleled by an increase in the T cell tropic coreceptor, CXCR4. Increases in NF-kappaB, TNFalpha, and CCR5 were consistent with the enhanced production of HIV-1 in MAg-treated adherent macrophage cultures as measured by HIV-1 p24 levels. Increased CCR5 was also detected in coinfected lymph nodes as compared with tissues with only HIV-1. The increased production of TNFalpha, together with elevated expression of CCR5, provide potential mechanisms for enhanced infection and replication of HIV-1 by macrophages in OI-infected cells and tissues. Consequently, treating OI may inhibit not only the OI-induced pathology, but also limit the viral burden.     

Risk factors of infected pancreatic necrosis, its microbiology and antibiotic treatment

Acute pancreatitis is associated with greater and smaller necrosis in 20% of the cases. The lethality rate of sterile and infected necrosis is 10 and 15-40%, respectively. The results of a retrospective and a prospective study in acute pancreatitis have been analyzed in this study. Twenty patients suffering from infected necrosis due to acute necrotising pancreatitis were selected into the retrospective study. They were divided into two groups: Group 1 (N = 10) survivors, Group 2 (N = 10) those who died. The fate of patients was determined by their age, the severity of pancreatitis, and the effectiveness of the operation. In a prospective study 63 patients were operated due to benign pancreatic disease with fluid collection. Microbiological samples were taken during surgery in every case. It could be stated that the Enterobacteriaceae spp. play the principal role in the infection, and the anaerobic bacteria occur sporadically. The omission of bacteriological sample taking during surgery frustrates the targeted antibiotic treatment. The blood culturing may have useful contribution. The targeted antibiotic therapy based on relevant microbiological sample taking is substantial complementary of the surgical intervention in the treatment of the inflammatory pancreatic diseases.     

Alcohol expectancies: effects of gender, age, and family history of alcoholism

Random samples taken from six recent textbooks and three older books in introductory psychology were analyzed with respect to linguistic style, emotional tone, and pattern of citation. Newer and older books, individual books, and categories of chapters within books were compared to each other. Analysis suggests that newer books are longer and linguistically more complicated. They also contain proportionally more citations, and more text pages devoted to social psychology and psychopathology than older books. There were several significant stylistic and emotional differences among books and some significant content differences among chapters.     

Role of G alpha q or G alpha o proteins in alpha 1-adrenoceptor subtype-mediated responses in Fischer 344 rat aorta

Previous studies showed that alpha-adrenoceptor (AR) stimulation with norepinephrine is more potent at eliciting contraction in aortas from 1-month-old Fischer 344 rats than from older rats and that this response is mediated by alpha 1b- and alpha 1d-AR subtypes in 1-month-old rats. We examined the G proteins responsible for alpha 1-AR-mediated contractile response and inositol phosphate accumulation in the aortas of 1-month-old Fischer 344 rats. Pertussis toxin (PTX) treatment (2.5 micrograms/ml for 4 hr) of aortic rings partially inhibited phenylephrine (PHE)-stimulated contraction and inositol phosphate accumulation, suggesting the involvement of PTX-sensitive and -insensitive G proteins. Specific antisera directed against G alpha q and G alpha o but not G alpha s and G alpha i precipitated specific alpha 1-AR binding sites labeled with 2-[beta-(4-hydroxy-3-[125I]iodophenyl)ethylaminomethyl]tetralone. The number of 2-[beta-(4-hydroxy-3-[125I]iodophenyl)ethylaminomethyl]tetralone binding sites precipitated by G alpha proteins was increased by activating membrane alpha 1-ARs with PHE. Moreover, PHE stimulated the palmitoylation of G alpha q and G alpha o, and this response was blocked by the alpha 1-AR antagonist prazosin. Characterization of the alpha 1-AR subtypes that couple to G proteins indicates that although aortic alpha 1a-, alpha 1b-, and alpha 1d-ARs were associated with G alpha q, alpha 1b-AR was also linked to G alpha o. These results suggest that alpha 1-ARs mediate the contractile response in rat aorta by coupling to both Gq protein and the PTX-sensitive G(o) protein.     

The glycemic index: flogging a dead horse?

Extensor tendon subluxation at the metacarpophalangeal joint occurs only rarely in patients without rheumatoid arthritis. Almost all reported cases involve disruption of the radial sagittal band with ulnar subluxation of the extensor tendon. A technique of sagittal band reconstruction is described that entails weaving a retrograde segment of extensor tendon upon itself after passing it through the deep transverse metacarpal ligament. Twenty-one sagittal band reconstructions were performed in 16 patients. This series included 18 cases of ulnar subluxation secondary to radial sagittal band disruption and 3 cases of radial subluxation secondary to ulnar sagittal band disruption. Using this technique, pain was eliminated in every case and there has been no recurrence of extensor tendon subluxation.     

Balloon aortic valvuloplasty

Sequence-tagged site (STS) content mapping in yeast artificial chromosomes (YACs) was used to cover the region deleted in two patients affected with X-linked lymphoproliferative disorder. The order of markers includes, centromere to telomere, DXS8009-DXS1206-DXS8078-DXS8044-DXS982- DXS6811-DXS8093-AFM240xblO- DXS75-DXS737-DXS100-DXS6-DXS1046-DXS803 8. The order of six major markers is confirmed by fluorescent in situ hybridization, and all the markers assigned by linkage mapping fall within a 1.6-cM interval. The contig comprises 90 clones containing 89 STSs, yielding a resolution of 50 kb; DNA in a gap just telomeric to DXS8044 has not been found in > 20 equivalents of YACs or bacterial clones. The two deletions were found to have centromeric breakpoints that lie close to DXS1206 and may be identical; the telomeric breakpoints are -150 kb apart, one falling between DXS737 and DXS100, the other between DXS100 and DXS1046. Several STSs near the breakpoints show weak amplification from more than one site; one gives products from three groups of YACs, and lie, respectively, within 50 kb of the centromeric and the two telomeric deletion borders. Such partially duplicated segments of DNA are candidates for involvement in the formation of the deletions.