Evaluation of RGS4 as a candidate gene for schizophrenia.

Several studies have suggested that the regulator of G-protein signaling 4 (RGS4) may be a positional and functional candidate gene for schizophrenia. Three single nucleotide polymorphisms (SNP) located at the promoter region (SNP4 and SNP7) and the intron 1 (SNP18) of RGS4 have been verified in different ethnic groups. Positive results have been reported in these SNPs with different numbers of SNP combinatory haplotypes. In this study, these three SNP markers were genotyped in 218 schizophrenia pedigrees of Taiwan (864 individuals) for association analysis. Among these three SNPs, neither SNP4, SNP7, SNP18 has shown significant association with schizophrenia in single locus association analysis, nor any compositions of the three SNP haplotypes has shown significantly associations with the DSM-IV diagnosed schizophrenia. Our results fail to support the RGS4 as a candidate gene for schizophrenia when evaluated from these three SNP markers.     

Impact of cadaveric organ donation on Taiwanese donor families during the first 6 months after donation

OBJECTIVE: Organ donation is a complex decision for family members of Asian donors. The impact of cadaveric organ donation on both Chinese and Western donor families has not been well investigated within a cultural framework. The purposes of this study were to follow Chinese family members' appraisal of their decision to donate organs, to explore the possible negative and positive impacts of organ donation on their family life, and to determine what help they expected from healthcare providers during the first 6 months after donation. METHODS: Twenty-two family members (10 men and 12 women) of cadaveric organ donors who signed consent forms at an organ transplant medical center in Taiwan participated in this project and completed in-depth interviews during the sixth month after donation. RESULTS: Participants were 25 to 56 years old (mean = 48.15 +/- 8.31 years). The type of kinship of the participants included the donor's parents, older sister, and spouse. Subjects reported several negative impacts: worry about the donor's afterlife (86%), stress due to controversy among family members over the decision to donate (77%), and stress due to others' devaluation of the donation (45%). Positive impacts reported by the subjects included having a sense of reward for helping others (36%), having an increased appreciation of life (32%), having closer family relationships (23%), and planning to shift life goals to the study of medicine (9%). Subjects expected the transplant team to provide information about organ recipients (73%), to submit the necessary documents so that family members could receive healthcare payments from the insurance company (68%), to help resolve legal proceedings and settlements associated with accidents (64%), and to not overly publicize their decision to donate (64%). CONCLUSIONS: Although all of the subjects reported that organ donation was the right decision, the decision to donate did not protect Taiwanese donor families from negative psychocognitive bereavement. The impacts of organ donation were affected by the subject's social cultural, spiritual, and legal context and the nature of their bereavement.     

Vancomycin-resistant enterococcal bacteremia: comparison of clinical features and outcome between Enterococcus faecium and Enterococcus faecalis.

BACKGROUND AND PURPOSE: Vancomycin-resistant enterococci (VRE) have emerged as important nosocomial pathogens. This study was conducted to clarify the clinical features and outcome of patients with vancomycin-resistant enterococcal bacteremia. METHODS: Patients with vancomycin-resistant enterococcal bacteremia treated at a medical center in northern Taiwan between November 1998 and July 2006 were reviewed. Clinical and bacteriological characteristics of Enterococcus faecium and Enterococcus faecalis were compared. RESULTS: Twelve patients (6 males and 6 females) were included for analyses. The mean age was 69.3 years (range, 40 to 86 years), and 8 cases (66.7%) were older than 65 years. All patients had underlying disease. Two patients received total hip replacement before development of VRE bacteremia. Twelve patients had prior exposure to broad-spectrum antimicrobial therapy. Ten patients had prior intensive care unit stay and prior mechanical ventilation before VRE bacteremia. All of the patients (n = 12) had an intravascular catheter in place. Bacteremia was caused by E. faecalis in 4 patients and by E. faecium in eight. The portals of entry included urinary tract (8.3%), skin, soft tissue and bone (41.7%) and unknown sources (50.0%). E. faecium showed a higher rate of resistance to ampicillin and teicoplanin than E. faecalis (87.5% vs 0.0%, p=0.01). The 60-day mortality rate was higher in patients with E. faecium bacteremia than E. faecalis bacteremia (62.5% vs 0.0%), although statistical significance was not obtained (p=0.08). CONCLUSIONS: VRE bacteremia may have an impact on the mortality and morbidity of hospitalized patients. Patients with bacteremia caused by vancomycin-resistant E. faecium had a grave prognosis, especially immunosuppressed patients. The prudent use of antibiotics and strict enforcement of infection control may prevent further emergence and spread of VRE.     

Remodelling of action potential and intracellular calcium cycling dynamics during subacute myocardial infarction promotes ventricular arrhythmias in Langendorff-perfused rabbit hearts

We hypothesize that remodelling of action potential and intracellular calcium (Ca_i) dynamics in the peri-infarct zone contributes to ventricular arrhythmogenesis in the postmyocardial infarction setting. To test this hypothesis, we performed simultaneous optical mapping of Ca_i and membrane potential ( V _m) in the left ventricle in 15 rabbit hearts with myocardial infarction for 1 week. Ventricular premature beats frequently originated from the peri-infarct zone, and 37% showed elevation of Ca_i prior to V _m depolarization, suggesting reverse excitation–contraction coupling as their aetiology. During electrically induced ventricular fibrillation, the highest dominant frequency was in the peri-infarct zone in 61 of 70 episodes. The site of highest dominant frequency had steeper action potential duration restitution and was more susceptible to pacing-induced Ca_i alternans than sites remote from infarct. Wavebreaks during ventricular fibrillation tended to occur at sites of persistently elevated Ca_i. Infusion of propranolol flattened action potential duration restitution, reduced wavebreaks and converted ventricular fibrillation to ventricular tachycardia. We conclude that in the subacute phase of myocardial infarction, the peri-infarct zone exhibits regions with steep action potential duration restitution slope and unstable Ca_i dynamics. These changes may promote ventricular extrasystoles and increase the incidence of wavebreaks during ventricular fibrillation. Whereas increased tissue heterogeneity after subacute myocardial infarction creates a highly arrhythmogenic substrate, dynamic action potential and Ca_i cycling remodelling also contribute to the initiation and maintenance of ventricular fibrillation in this setting.     

Characterization of a strain-specific monoclonal antibody to hepatitis delta virus antigen

Sequences of the hepatitis delta virus (HDV) vary to different degrees among isolates. A monoclonal antibody, designated as HP6A1, against the antigen of HDV (HDAg) has been characterized for its specificity. HP6A1 bound to HDAg of isolate 25 (genotype I) that was used for immunization, but not to others of both genotypes I and II. The epitope recognized by HP6A1 was then determined by a phage library displaying various heptapeptides. A consensus peptide deduced has the best match with that of residues 4-10 of HDAg (isolate 25). To confirm the phage mapping result, Escherichia coli recombinant proteins containing different lengths and various segments of HDAg (isolate 25) were constructed. The shortest HDAg segment contained in the fusion protein that reacted with HP6A1 was residues 1-10. When this peptide was added to the N-terminus of a heterologous protein engineered for eucaryotic expression, the fusion protein was detected by HP6A1. It is concluded that HP6A1 recognizes an epitope located at the N-terminus of HDAg (isolate 25). Since viruses of quasi-species exist in natural infections, a question of how different viral strains interact in vivo remains to be explored. The highly specific MAb opens a possibility to examine the fate of one strain in the presence of other related species in a cell transfection system.     

Continuous and online analysis of heart rate variability

Spectral analysis of heart rate variability provides a probe to assess the function of the sympathetic and parasympathetic nervous systems. Time-frequency analysis of heart rate variability is useful for investigating autonomic nervous function in patients with syncope or non-sustained ventricular tachycardia, or in anaesthesia, etc. In this paper, we developed an algorithm for continuous and online analysis of heart rate variability. The algorithm was simulated and evaluated in MATLAB, and implemented on the digital signal processor. The electrocardiogram signals from MIT/BIH arrhythmia database and one patient with syncope demonstrate the capability of the proposed method in the continuous and online analysis of heart rate variability.     

Immunohistochemical localization of parathyroid hormone-related protein in parathyroid adenoma and hyperplasia

Parathyroid hormone-related protein (PTHrP) is invoked as the cause of humoral hypercalcaemia of malignancy (HHM); it is contained in the keratinocyte layer of normal skin; and there is evidence that is is produced by fetal parathyroids. Antibodies against synthetic PTHrP peptides have been raised in rabbits and sheep. This immunohistochemical study has found that primary parathyroid adenomata and hyperplastic glands from patients with chronic renal failure stain positively with antisera against PTHrP(1-34) and PTHrP(50-69). Primary hyperplastic glands are negative. No staining with anti-PTHrP(106-141) antiserum could be detected immunohistochemically in any of the parathyroid adenomata or hyperplasia.     

Preparation of a recombinant cDNA library from poly(A+) RNA of the Alzheimer brain. Identification and characterization of a cDNA copy encoding a glial-specific protein

Studies were undertaken to assess the extent to which messenger RNA prepared from the postmortem Alzheimer's disease (AD) brain can be used for the successful preparation of a recombinant cDNA library. Initial experiments focused on the glial-specific marker glial fibrillary acidic protein (GFAP) since GFAP expression appeared to be a model for further studies on mRNAs that may continue to be expressed at high levels in the vicinity of lesioned sites in the AD brain. An AD cDNA library, prepared in the lambda gt11 expression vector system contained GFAP-specific recombinants. One of these was sequenced and the insert was shown to exhibit 88% homology with the similar sequence from mouse GFAP. As established by Northern blots, the size of the GFAP mRNA prepared from the routinely acquired postmortem AD cortex, approximately 2.7 kb, was the same as from a neurologically normal control brain. These results agree with earlier studies on GFAP mRNA from fresh mouse brain. The results demonstrate that in the postmortem AD brain, astroglial-specific mRNA remains sufficiently stable for molecular genetic analysis and may serve as a useful model for examining the genetic expression of mRNAs that may be related to the molecular pathogenesis and the etiology of AD.     

An autopsy-proved case of AIDS in Taiwan

The first case of AIDS positively identified in a non-foreigner in Taiwan was a 25-year-old unmarried male who had practiced homosexuality for ten years. The patient began to have abdominal pain accompanied with loose stools and weight loss in June 1985, followed by fever, cough, headache, dizziness, and loss of memory. Facial hyperpigmentation and extensive oroesophageal candidiasis were noted. Laboratory studies showed severe lymphopenia with a reversed T-helper to T-suppressor ratio, cutaneous anergy and polyclonal gammopathy. Human immunodeficiency virus (HIV) antibodies were positive by ELISA and Western blot, and the virus was isolated from the blood. At autopsy, disseminated cytomegalovirus infection, extensive CNS toxoplasmosis and early lesions of Kaposi's sarcoma were demonstrated. The detection of HIV in the adrenal medulla supports the consensus that the virus is neurotropic.     

Identification of carmine allergens among three carmine allergy patients

BACKGROUND: There have been several reports of carmine allergy; however, identification of the responsible carmine allergens has not been widely documented. METHODS: Three female patients presented with a history of anaphylaxis and/or urticaria/angioedema after ingestion of carmine-containing foods. All three patients had 4+ skin prick tests to carmine. Among them, two patients were confirmed to have carmine allergy by blinded, placebo-controlled food challenges to carmine. SDS-PAGE of cochineal insects and carmine, immunoblotting for IgE antibody with sera from all three patients, and immunoblotting inhibition with carmine were performed. RESULTS: SDS PAGE of minced cochineal insects revealed several protein bands of 23-88 kDa. Several of these bands were variably recognized by our three patients' sera, and this reactivity was inhibited by carmine. Although no protein bands could be visualized on SDS-PAGE of carmine in Coomassie brilliant blue staining, three protein bands were recognized by two of the three patients' serum. CONCLUSIONS: These results suggest that commercial carmine retains protein-aceous material from the source insects. These insect-derived proteins (possibly complexed with carminic acid) are responsible for IgE-mediated carmine allergy. Patient reactivity to these proteins may vary.