Transient hyperphosphatasaemia in an adult with pre-existing liver disease.
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Alkaline Phosphatase↗
Biomedical subjects
T Wong
Publications and source records attributed to T Wong.
[Time trend of mortality rates of cerebrovascular diseases in Hong Kong].
OBJECTIVE: To describe the time trend of mortality rates of cerebrovascular diseases (CVD) in Hong Kong for the period of 1976 to 1995, and to compare them with those in the more developed countries around the world. METHODS: Mortality rates of CVD were standardized directly using world standard population in 1961. Annual percent changes of mortality rates of CVD were estimated with a non-linear regression. Birth-cohort analysis was carried out at an interval of five-year of age to compare their age-specific mortality rates of CVD in different birth cohorts. Time trend of cause-specific mortality rates of CVD both in males and females was fitted with a simple linear regression model. RESULTS: Considerable downward trend of CVD mortality was observed during the past twenty years. Mortality rates among men and women decreased by 50.96% and 37.85% in 1995, as compared to those in 1976, respectively. Although in general, a greater trend in CVD mortality was observed during the last 10 years, as compared with that in the previous 10 years, an annual increase in CVD mortality of 1.34% was found among males aged 35 to 44 years during the latter 10 years. CVD mortality for both males and females decreased steadily by 1% per year. CVD mortality for females will catch up with that for males by the year of 2013, if such a trend continues. Birth-cohort analysis showed that those born more recently at the same age-group had lower mortality of CVD (except for those born after 1955). Data from hospital admission showed that improvement in the treatment for CVD could have contributed partly to the decrease in its mortality. CONCLUSION: Time trend of mortality of CVD in Hong Kong was similar to that in many other economically developed areas around the world.
Adult↗
Gating of CaMKII by cAMP-regulated protein phosphatase activity during LTP.
Long-term potentiation (LTP) at the Schaffer collateral-CA1 synapse involves interacting signaling components, including calcium (Ca2+)/calmodulin-dependent protein kinase II (CaMKII) and cyclic adenosine monophosphate (cAMP) pathways. Postsynaptic injection of thiophosphorylated inhibitor-1 protein, a specific inhibitor of protein phosphatase-1 (PP1), substituted for cAMP pathway activation in LTP. Stimulation that induced LTP triggered cAMP-dependent phosphorylation of endogenous inhibitor-1 and a decrease in PP1 activity. This stimulation also increased phosphorylation of CaMKII at Thr286 and Ca2+-independent CaMKII activity in a cAMP-dependent manner. The blockade of LTP by a CaMKII inhibitor was not overcome by thiophosphorylated inhibitor-1. Thus, the cAMP pathway uses PP1 to gate CaMKII signaling in LTP.
Animals↗
Surgical treatment of low-grade gliomas in the intraoperative magnetic resonance imager.
Radical resection of low-grade gliomas can decrease the incidence of recurrence, the time to tumor progression, and the incidence of malignant transformation. The authors present a series of 25 patients who underwent craniotomy and resection of low-grade tumor in an intraoperative magnetic resonance (MR) imager. This is an open configuration 0.5-tesla imager developed by The Brigham and Women's Hospital and General Electric, in which a patient can be placed to undergo surgery. Gross-total removal was accomplished under real-time image guidance. These intraoperative images allow definitive localization and targeting of the lesions and accommodate anatomical changes that may occur during surgery. The authors consistently found that the extent of abnormality seen on the intraoperatively obtained films of resection was larger than that apparent in the surgical field of view alone. Intraoperative imaging made accurate surgical identification of these abnormal areas and subsequent resection possible. Patients with tumors adjacent to or within motor or language cortex underwent resection while awake, with monitoring of neurological function. In these cases, an aggressive resection without increased neurological morbidity was accomplished using the image guidance in conjunction with serial testing. A 1-month postoperative MR image was obtained in all patients. These correlated with the final intraoperative images obtained after the resection was completed. Only one patient had a mild postoperative deficit that remained at the 1-month follow-up examination. As the long-term outcome in patients with low-grade gliomas has been shown to correspond to the degree of resection, surgical resection in which intraoperative MR imaging guidance is used can be an invaluable modality in the treatment of these tumors.
Journal Article↗
Metabotropic glutamate receptors limit adenylyl cyclase-mediated effects in rat hippocampus via protein kinase C.
Glutamate receptors of the metabotropic type (mGluRs) activate protein kinase C in hippocampus, but few physiological functions of this pathway are known. The present data show that mGluRs utilize protein kinase C to inhibit another second messenger system, the adenylyl cyclase pathway, in neurons of the CA1 area of hippocampus. Activation of mGluRs prevented beta-adrenergic receptors, which couple to adenylyl cyclase, from blocking the slow Ca2+-dependent afterhyperpolarization (AHP). Since the afterhyperpolarization modulates neuronal responsiveness, crosstalk between protein kinase C and the adenylyl cyclase pathway is likely to have physiological consequences. Moreover, mGluRs themselves block the afterhyperpolarization, so the observed interference with the beta-adrenergic response constitutes a hierarchical relationship in which mGluRs are dominant over beta-adrenergic receptors.
Adenylyl Cyclases↗
Defining the outcome of immunosuppression withdrawal after liver transplantation.
Successful immunosuppression withdrawal should benefit the natural history of organ transplantation patients. To identify the clinical hazards of removing drug treatment and possible characteristics that predict a favorable outcome in long-term liver recipients, immunosuppression was withdrawn completely and the clinicopathological outcome documented in 18 liver recipients. Indication for transplantation, HLA matching, early rejection history, and presence of microchimerism were examined as predictors of outcome. Chimerism was determined by polymerase chain reaction-based examination for donor-specific HLA-DRB1 alleles and Y-gene-specific nucleotide sequences. At 3 years, 5 patients (28%) remained completely off immunosuppression; 12 patients (67%) experienced histological graft changes: acute rejection in 4, portal tract inflammation/hepatitis in 7, and necrosis in 1. Hepatitis B or C viral infections did not account for the nonrejection patterns. Unmasking of systemic disorders occurred. Chimerism, demonstrated in 7 patients (39%), with skin the optimal tissue, was not associated with tolerance. Parameters associated with successful drug withdrawal were transplantation for non-immune-mediated liver disorders, fewer donor-recipient HLA A, B, and DR mismatches, and a low incidence of early rejection. Immunosuppression withdrawal is a feasible option in a proportion of selected liver recipients, but identification of tolerant patients remains imprecise.
Adult↗
Tolerance and latent cellular rejection in long-term liver transplant recipients.
Tolerance develops in a proportion of long-term liver transplant recipients but currently cannot be identified before an attempt at withdrawal from immunosuppression therapy. In the present study, we have examined the immunophenotypic characteristics of the cellular infiltrate in portal tracts and lobules as observed in liver biopsy specimens in relation to the outcome of subsequent withdrawal from immunosuppression therapy. Cryostat biopsy specimens from 27 long-term recipients before drug withdrawal, and from 10 patients with recent transplants who were having acute rejection, were analyzed. Immunohistochemical staining was performed for CD3+ (pan T cell), CD8+ (cytotoxic), CD4+ (helper), CD45RO+ (memory), CD45RA+ (naive), CD56+ (natural killer), CD68+ (macrophage), and CD8+ perforin+ cells. Fewer CD8+ and CD3+ cells were present in the lobular areas of biopsy specimens from patients who were successfully withdrawn from immunosuppression therapy (n = 6) compared with biopsy specimens from patients with nontolerant grafts (n = 9; 15 vs. 23 cells/high-power field [hpf] [P < .01] and 16 vs. 26 cells/hpf [P < .03], respectively) or biopsy specimens obtained during acute rejection (15 vs. 31 cells/hpf [P < .01] and 16 vs. 32 cells/hpf [P < .01]). Cell frequencies in the biopsy specimens of nontolerant long-term patients were similar to those found with acute rejection. Immunophenotyping the lobular inflammation within long-term liver allografts assists in identifying those patients in whom drug withdrawal is likely to be unsuccessful and in whom it is postulated a form of inactive, latent cellular rejection exists.
Adolescent↗
Differential signaling and hierarchical response thresholds induced by an immunodominant peptide of myelin basic protein and an altered peptide ligand in human T cells.
Changes in peptide antigen concentration or structure can have a profound effect on T cell responsiveness by inducing selected T cell effector functions. In this study, we have compared the biological responses of an MBP83-99-specific human Th0 T cell clone (TCC) stimulated with increasing concentrations of native peptide or an altered peptide ligand (APL). Our results show that the hierarchy of response thresholds for proliferation and cytokine secretion is similar for native peptide and APL. However, because a much higher concentration of the APL is required to evoke the same degree of response, the cytokine profile is shifted towards a Th2-like response relative to the same concentration of native peptide. In addition, we observed qualitative differences in TCR signal transduction triggered by native peptide and a weak agonist APL even at concentrations that elicit similar biological responses. Thus, the relationship between TCR signaling and biological responses may be more complex than previously recognized.
Adaptor Proteins, Signal Transducing↗
Fungemia due to Hormonema dematioides following intense avian exposure.
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AIDS-Related Opportunistic Infections↗
Human leptospirosis in the Seychelles (Indian Ocean): a population-based study.
A leptospirosis surveillance program was carried out for 12 months on the entire population of the Seychelles. Diagnosis was assessed by both microagglutination test and polymerase chain reaction (PCR) assay. In this population of 74,331, leptospirosis was clinically suspected in 125 subjects and confirmed in 75 patients (incidence of 101 per 100,000; 95% confidence interval = 79-126). Leptospirosis was more frequent in middle-aged males with environmental exposure. Eight serogroups were identified and Icterohaemorrhagiae (31%) and Hurstbridge (20%) were the most frequent. Hurstbridge, a recently identified new serogroup, was implicated in severe cases and death. Influenza-like forms accounted for 37% of the cases while jaundice, acute renal failure, and pulmonary hemorrhage occurred in 52%, 28%, and 19%, respectively. Death occurred in six patients and was related to pulmonary hemorrhage. The PCR result was positive after completion of treatment in eight patients, suggesting that the administered five-day course of penicillin may be inadequate to eradicate the bacteria.
Adolescent↗
Caring in context: caring practices in a sample of Hong Kong nurses.
In an effort to place the international literature and research in nursing in a Chinese cultural context a study was commenced to examine the caring practices of nurses in Hong Kong. In view of a recent study (Wilkes & Wallis, 1993) which utilised Roach's 5Cs of caring (Roach, 1987, 1992), a pilot study was commenced on a sample of 77 Hong Kong Registered Nurses studying a Diploma of Nursing. An open ended questionnaire was designed which asked nurses to respond to questions about caring in general and the 5Cs: compassion, competence, confidence, conscience and commitment. The questions asked what each of the concepts meant to them as a nurse. Data was analysed into themes based on key words for each of the six areas revealing that the sample of Hong Kong nurses viewed caring in a similar light to those in overseas studies. The sample highlighted compassion and competence as their major features and it is suggested that methodological problems may have inhibited a deeper analysis of their caring attributes and behaviours. When asked to expand on the 5 Cs in terms of their own practice they were able to supply themes which were closely related to Roach's definitions but which may have been more 'textbook' in their origin and certainly lacked a richness of response. The paucity of responses in terms of clarity and richness of data, followed by discussions with the participants led to conclusions about the methodological issues of cross-cultural research and recommendations for future research are made. Highlighted are the problems with attempting to use concepts such as the 5 Cs across cultures and the problems encountered with translation of concepts related to caring from Chinese into English, and vice-versa. The study has provided some insights into the concepts of caring in Hong Kong Chinese nurses. In the light of advances in China and unification of previously separate countries these findings provide and offer insights into nursing in China and are encouraging for future research.
Clinical Competence↗
Monte Carlo dosimetry of the microselectron HDR 192Ir brachytherapy source using MCNP4A.
This study examines the transverse radial dose distribution around the Nucletron MicroSelectron high dose rate (HDR) 192Ir brachytherapy source using the Monte Carlo radiation transport code MCNP (Monte Carlo N Particle) version 4A. The geometry modeled consisted of an identical simulation of the geometry of the MicroSelectron HDR source within the centre of a cylindrical water phantom of 80 cm diameter and height. Doses were calculated at 0.1 cm intervals in the 1 cm closest to the source, whilst extending to 1 cm intervals 15 cm from the source. Conversion to the clinically relevant unit of air-kerma strength to describe source activity enables absolute comparison of Monte Carlo dose calculations to current treatment planning computer results. Most HDR brachytherapy planning computers utilise algorithms based on a point source with attenuation and scatter corrections based on the Van Kleffen and Starr or Meisberger equations. Significant differences between the planning computer algorithms and the Monte Carlo dose calculations occur in the near field (radius less than 1 cm) and the far field (radius greater than 8 cm) which in some cases may have important clinical consequences. These results are consistent with Monte Carlo calculations of previous authors examining the MicroSelectron HDR 192Ir source and also show that far field uncertainties are increased as the size of the phantom is reduced to a more realistic patient size.
Brachytherapy↗
Replacement of linoleic acid with alpha-linolenic acid does not alter blood lipids in normolipidaemic men.
The effect of partial dietary replacement of linoleic acid (18:2n-6; linoleic acid-rich diet) with alpha-linolenic acid (18:3n-3; alpha-linolenic acid-rich diet) on plasma lipids was investigated in twenty-nine healthy young men. After a 2-week stabilization period subjects were randomly assigned to either the alpha-linolenic acid-rich diet group (n 15), receiving a mean of 10.1 g of alpha-linolenic acid and 12.1 g of linoleic acid/d, or the linoleic acid-rich diet group (n 14), receiving a mean of 1.0 g of alpha-linolenic acid and 21.0 g of linoleic acid/d, for a 6-week test period. Blood samples were taken at the commencement of the stabilization period and at the start (week 0), midpoint (week 3) and endpoint (week 6) of the test period and plasma lipids analysed. The changes occurring on the linoleic acid-rich diet and alpha-linolenic acid-rich diet were compared but no significant differences in the changes in plasma total cholesterol, LDL-cholesterol, HDL-cholesterol, the subfractions HDL2 and HDL3 or triacylglycerols were found. These results indicate that dietary replacement of linoleic acid with alpha-linolenic acid in the diet of healthy male subjects offers similar cardioprotective benefits with respect to lipid metabolism.
Adolescent↗
Purification and microsequencing of hyaluronidase isozymes from human urine.
We recently cloned the major hyaluronidase of human plasma, which we termed HYAL1. All hyaluronidase activity could be purified from human urine on an anti-HYAL1 monoclonal antibody column. However, urine contains two hyaluronidases of 57 kDa and 45 kDa, whereas plasma only contains the 57 kDa activity. Microsequencing confirmed that both urinary isozymes have N-termini identical to plasma hyaluronidase, but a second N-terminus was found in the smaller isozyme, apparently derived from the terminal 25 amino acids of HYAL1, at the C-terminus. The two polypeptides of the 45 kDa isozyme resulting from endoproteolytic cleavage of the 57 kDa isoform are presumably linked by disulfide bonds. Sperm contains two isozymes of the testicular hyaluronidase, PH-20, and the lower molecular weight isozyme is believed to be an endoproteolytically processed form of the larger protein. Analogously to PH-20, the smaller isozyme of HYAL1 is likely to be a proteolytically processed product of the larger isozyme.
Amino Acid Sequence↗
Clinical characteristics affecting the outcome of liver retransplantation.
BACKGROUND: The outcome of retransplantation remains unsatisfactory when compared with primary transplantation of the liver. The aim of the present study was to determine which preoperative clinical and laboratory risk variables are implicated in the poorer outcome. METHODS: The preoperative status of 70 retransplanted patients was compared with a group of 303 time-matched recipients receiving their first graft. RESULTS: Survival at 1 year was reduced in the retransplant versus the primary transplant group (50% vs. 80%, P<0.001). Preoperatively older age, high United Network of Organ Sharing score, inpatient status, elevated bilirubin, and creatinine levels were associated with increased mortality after a second transplant. Preoperatively, the retransplant group had higher encephalopathy grades, were more likely to be inpatients, and had higher serum creatinine, bilirubin, and white cell levels than the primary recipients (P<0.05 in all cases). The median length of inpatient stay was longer after the second transplant (25 vs. 19 days, P<0.001). CONCLUSIONS: These factors assist in the stratification of patients awaiting retransplantation; however, the outcome of this procedure is only likely to be improved with an earlier identification of the patients who require it, along with an increased priority in organ allocation.
Adolescent↗
Purification, cloning, and expression of human plasma hyaluronidase.
Hyaluronidase was purified from human plasma using Triton X-114 phase extractions and ion-exchange chromatography. Monoclonal antibodies generated against the purified protein by a novel screening assay were utilized to isolate homogeneous enzyme for microsequencing. The amino acid sequences obtained matched a cDNA in the Expressed Sequence Tag database which, with 5'-RACE-PCR, was used to clone the plasma hyaluronidase gene, termed Hyal-1. Hyal-1 codes for a protein of 435 amino acids that is over 40% identical to PH-20, a sperm-specific hyaluronidase. Unlike PH-20, which is only expressed in testis, transcripts of Hyal-1 were found in multiple tissues. Hyal-1 stably expressed in human embryonic kidney cells resulted in a 3,000 fold increase of secreted immunoreactive hyaluronidase activity that was biochemically indistinguishable from human plasma hyaluronidase. By immunological, molecular and biochemical criteria, we conclude that Hyal-1 is the predominant hyaluronidase found in human plasma.
Amino Acid Sequence↗
Stress and autoimmunity: the neuropeptides corticotropin-releasing factor and urocortin suppress encephalomyelitis via effects on both the hypothalamic-pituitary-adrenal axis and the immune system.
Corticotropin-releasing factor (CRF) exerts a major role in the stress response. Both CRF and urocortin, a newly discovered neuropeptide homologous to CRF, suppressed experimental autoimmune encephalomyelitis (EAE). Suppression of paralysis with CRF involved stimulation of the hypothalamic-pituitary-adrenal axis and inhibitory effects on an encephalitogenic T cell line. While CRF increased glucocorticoid production, which is known to block EAE, it also suppressed EAE in adrenalectomized rats, where glucocorticoid stimulation via CRF plays no role. Moreover, the encephalitogenicity of a T cell line exposed to CRF in vitro was reduced. Stress may influence autoimmune disease through the hypothalamic-pituitary-adrenal axis and directly via the immune system.
Animals↗
Immunosuppressive phenotype of corticotropin-releasing factor transgenic mice is reversed by adrenalectomy.
Stress elicits a wide range of physiological changes involving the nervous, endocrine, and immune systems. Corticotropin-releasing factor (CRF) plays a key role in orchestrating this response, activating both the sympathetic nervous system and the hypothalamic-pituitary-adrenal axis, resulting in release of corticosteroids. The present study examines the immunological phenotype and responsiveness of CRF-transgenic (CRF-Tg) mice. The immune system of the CRF-Tg animals has profound changes compared to littermate controls, including a marked reduction in both cell number and immune responsiveness. There were also phenotypic changes in the lymphocytic composition of the various lymphoid organs, most notably in the spleen, where CRF-Tg mice had a greater percentage of T lymphocytes compared to littermate controls. Adrenalectomy of CRF-Tg reversed the immunological phenotype observed and restored immune responsiveness. These results demonstrate that CRF overexpression leads to profound impairment on lymphocyte development and function mediated via corticosteroids.
Adrenalectomy↗