Creutzfeldt--Jakob Disease in Recipients of Human Growth Hormone in the United Kingdom: A Clinical and Radiographic Study

In the past 3 years there have been five further cases, in additionto one case reported in 1985, of Creutzfeldt-Jakob disease inrecipients of human growth hormone in the United Kingdom. Theclinical findings of two of these cases are described, demonstratinga typical presentation with a predominantly cerebellar syndromeat onset which is not commonly a presenting feature of sporadicCreutzfeldt-Jakob disease. In one case a ^99mTc hexamethylpropylenaminesingle photon emission tomographic scan showed marked impairmentof tracer uptake in the basal ganglia and cerebral cortex ata time when the clinical picture was predominantly cerebellar.This technique may be useful in early diagnosis. In the othercase post mortem examination of the brain showed prominent amyloiddeposition in the cerebellum, which has not been described previouslyin pituitary-hormone related Creutzfeldt-Jakob disease. Thepreviously published cases of growth hormone-related Creutzfeldt-Jakobdisease are reviewed and reasons for the particular clinicalpattern seen are discussed.     

YC-1 suppresses constitutive nuclear factor-kappaB activation and induces apoptosis in human prostate cancer cells

Although the indazole compound, YC-1, is reported to exert anticancer activities in several cancer cell types, its target and mechanism of action have not been well explored. The objectives of this study were to ascertain whether YC-1 directly induces apoptosis in prostate cancer cells and to explore the mechanism(s) whereby YC-1 causes cell death. Hormone-refractory metastatic human prostate cancer PC-3 cells were selected for this study. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide assay indicated that YC-1 suppresses growth of PC-3 cells in a concentration-dependent and time-dependent manner. Apoptosis was determined using 4',6-diamidino-2-phenylindole staining, and cell cycle progression was examined by FACScan flow cytometry. YC-1 treatment showed chromatin condensation and increased the percentage of PC-3 cells in the hypodiploid sub-G0-G1 phase, indicative of apoptosis. Additionally, exposure to YC-1 was found to induce activation of caspase-3 and cleavage of poly(ADP-ribose) polymerase. Translocation and activation of nuclear factor-kappaB (NF-kappaB) were determined by immunofluorescent staining and ELISA, respectively. The results showed that YC-1 abolished constitutive nuclear translocation and activation of NF-kappaB/p65. Furthermore, inhibition of inhibitor of kappaBalpha (IkappaBalpha) phosphorylation and accumulation of IkappaBalpha were observed. The antitumor effects of YC-1 were evaluated by measuring the growth of tumor xenografts in YC-1-treated severe combined immunodeficient mice. The volumes of PC-3 tumors produced in severe combined immunodeficient mice were observed to decline significantly after treatment with YC-1 compared with vehicle controls. We concluded that the antitumor effects of YC-1 in PC-3 cells include the induction of apoptosis and the suppression of NF-kappaB activation. Given these unique actions, further investigations of the effects of YC-1 against hormone-refractory prostate cancer are warranted.     

Blood screening for non-A, non-B hepatitis by hepatitis C virus antibody assay

Hepatitis C virus (HCV) antibody was detected in 1499 donor sera by radioimmunoassay using an antigen expressed in yeast from a cDNA clone of the HCV genome. Eighteen samples over 4200 counts per minute (cpm) were considered to contain infectious HCV because these recipients developed typical posttransfusion non-A, non-B hepatitis after transfusion. The antibody-positive sera were all within the normal range of ALT levels. This assay system is thus useful for the screening for blood transfusion.     

Development of specific receptors for N-formylated chemotactic peptides in a human monocyte cell line stimulated with lymphokines

A human monocyte-like cell line, U937, when grown in continuous culture, does not secrete lysosomal enzymes or migrate towards chemotactic factors. When the cells are stimulated by lymphokines, however, they develop the ability both to migrate directionally and to secrete enzymes in response to several types of chemoattractants. The development, by stimulated cells, of chemotactic and secretory responses to one class of chemoattractants, the N- formylated peptides, is accompanied by the appearance on the cells of specific binding sites for these substances. Using tritiated N-formyl- methionyl-leueyl-phenylalanine (fMet-Leu-[(3)H]Phe) as a ligand, it was determined that unstimulated U937 cells possess no detectable binding sites. However, after stimulation with lymphocyte culture supernates for 24, 48, and 72 h, they developed 4,505 (+/-) 1,138, 22,150(+/-) 4,030, and 37,200 (+/-) 8,000 sites/cell, respectively. The dissociation constants for the interaction of fMet-Leu-[SH]Phe with the binding sites were approximately the same regardless of stimulation time and ranged between 15 and 30 nM. The binding of fMet-Leu-[(3)H]Phe by stimulated U937 cells was rapid and readily reversed by the addition of a large excess of unlabeled peptide. The affinity of a series of N-formylated peptides for binding to U937 cells exactly reflected the potency of the peptides in inducing lysosomal enzyme secretion and chemotaxis. The availability of a continuous human monocytic cell line that can be induced to express receptors for N-formylated peptides will provide a useful tool not only for the characterization of such receptors but also for the delineation of regulatory mechanisms involved in cellular differentiation and the chemotactic response.     

Resuscitation from experimental traumatic brain injury by agmatine therapy

Both nitric oxide and glutamate contribute to ischaemic brain injury. Agmatine inhibits all isoforms of nitric oxide synthase and blocks N-methyl-d-aspartate receptors. In this study, we gave agmatine intraperitoneally and assessed its effect on fluid percussion brain injury in rats. Anaesthetised rats, immediately after the onset of fluid percussion traumatic brain injury (TBI), were divided into two major groups and given the vehicle solution (1mL/kg) or agmatine (50mg/kg) intraperitoneally. Mean arterial pressure, intracranial pressure, cerebral perfusion pressure, and levels of glutamate, nitric oxide, lactate/pyruvate ratio, and glycerol in hippocampus were monitored continuously within 120min after TBI. The weight loss was determined by the difference between the first and third day of body weight after TBI. The maximal grip angle in an inclined plane was measured to determine motor performance whereas the percent of maximal possible effect was used to measure blockade of proprioception. The triphenyltetrazolium chloride staining procedures were used for cerebral infarction assay. Compared to those of the sham-operated controls, the animals with TBI had higher values of extracellular levels of glutamate, nitric oxide, lactate-to-pyruvate ratio, and glycerol in hippocampus and intracranial pressure, but lower values of cerebral perfusion pressure. Agmatine administered immediately after TBI significantly attenuated the TBI-induced increased hippocampal levels of glutamate, nitric oxide, lactate-to-pyruvate ratio, and glycerol, intracranial hypertension, and cerebral hypoperfusion. In addition, the TBI-induced cerebral infarction, motor and proprioception deficits, and body weight loss evaluated 3 days after TBI were significantly attenuated by agmatine therapy. The present data indicate that agmatine may attenuate TBI by reducing the excessive accumulation of both glutamate and nitric oxide in the brain.     

Amphiphysin IIm is required for survival of Chlamydia pneumoniae in macrophages

Macrophages play a critical role in both innate and acquired immunity because of their unique ability to internalize, kill, and degrade bacterial pathogens through the process of phagocytosis. The adaptor protein, amphiphysin IIm, participates in phagocytosis and is transiently associated with early phagosomes. Certain pathogens, including Chlamydia pneumoniae, have evolved mechanisms to subvert macrophage phagosome maturation and, thus, are able to survive within these cells. We report here that, although amphiphysin IIm is usually only transiently associated with the phagosome, it is indefinitely retained on vacuoles containing C. pneumoniae. Under these wild-type conditions, C. pneumoniae do not elicit significant nitric oxide (NO) production and are not killed. Abrogation of amphiphysin IIm function results in C. pneumoniae-induced NO production and in the sterilization of the vacuole. The data suggest that C. pneumoniae retains amphiphysin IIm on the vacuole to survive within the macrophage.     

Antimicrobial Activity of Several Antibiotics and a Sulfonamide Against Chlamydia trachomatis Organisms in Cell Culture

Serum interferon activity was determined in 12 cynomolgus and 12 rhesus monkeys injected intravenously once daily for 10 days with from 0.1 to 6.0 mg of a stabilized polyriboinosinic acid . polyribocytidylic acid complex per kg, composed of polyriboinosinic acid . polyribocytidylic acid, poly-1-lysine, and carboxymethylcellulose [poly(ICLC)]. Interferon activity was detected 2 h after the first injection, with maximum activity occurring 8 h after the second injection. A period of hyporesponsiveness occurred after the third injection of poly(ICLC) in all monkeys and lasted until the sixth injection in the rhesus monkeys, when interferon activity again became more elevated. The delayed rebound was not as apparent in cynomolgus monkeys. Rhesus monkeys injected with 6 mg/kg did not exhibit serious side effects.     

Antimicrobial resistance of Streptococcus pneumoniae isolated in Taiwan: an island-wide surveillance study between 1996 and 1997

Between August 1996 and July 1997, 550 clinically significant Streptococcus pneumoniae isolates were collected from 14 geographically separate laboratories in Taiwan. These isolates were serotyped and MICs were determined by agar dilution. Among serotypes covered by the 23-valent vaccine, types 19F, 19A, 23F, 23A and 6B dominated, comprising 255 isolates; among non-vaccine serotypes, types 35, 39, 34, 13 and 31 dominated, comprising 118 isolates. Of the 550 isolates, 310 (56.4%) were resistant to penicillin G (MIC 0. 12 mg/L), 238 (43.3%) with intermediate resistance (MIC 0.12-1 mg/L) and 72 (13.1%) with high-level resistance (MIC 2 mg/L). Most non-susceptible pneumococci were of serotypes 19F and 23F; non-susceptible isolates of these serotypes were distributed across all of Taiwan. Fourteen other antibiotics were tested; 83% of the isolates were resistant to tetracycline, 78% to azithromycin, 74% to erythromycin, 54% to clindamycin and 23% to chloramphenicol. Thus, macrolides can no longer be used as first line agents to treat pneumococcal infections in Taiwan. Multi-resistance (isolates resistant to three or more chemically unrelated antibiotics) was found in each serotype or group, but mostly in types 19F and 23F. The emergence of such strains complicates antibiotic selection, but both types are covered by the 23-valent vaccine, as were 82% of the isolates from blood and eight of the nine from cerebrospinal fluid. Good antibiotic control and appropriate use of this vaccine may improve the current problem in Taiwan, especially for the elderly.     

M2 macrophage subset decrement is an indicator of bleeding tendency in pediatric dengue disease

Background/purpose

Dengue disease is widespread in tropical and sub-tropical regions. Severe dengue infection is characterized by plasma leakage, fluid accumulation, severe bleeding, or vital organ impairment. Bleeding is a critical complication of dengue disease. However, the biomarkers of dengue disease are still unknown. Macrophages have a distinct polarization phenotype related to M1/M2 classification. Macrophage polarization toward the pro-inflammatory M1 phenotype is considered critical for efficient antiviral immune responses, whereas the anti-inflammatory M2 phenotype is considered essential for tissue remodeling. We investigated macrophage polarization patterns in the peripheral blood of pediatric patients with dengue disease.

Vancomycin-resistant Enterococcus faecium at a university hospital in Taiwan, 2002–2015: Fluctuation of genetic populations and emergence of a new structure type of the Tn1546-like element

Background/purposes

Vancomycin resistance increased significantly to 31.3% among Enterococcus faecium in 2006 and remained high thereafter at a university hospital in Taiwan. A longitudinal study was retrospectively conducted to characterize these vancomycin-resistant E. faecium (VRE-fm).