Background Most cultures believe in ghosts and for the Chinese, the seventh lunar month-the ghost month-causes particular concern. 'The gates of hell' are open for the first 14 days of the month which allows the restless ghosts of people who were hungry when they died to haunt the living. In this study, it was hypothesised that if the notion that ghosts are out to harm the living could affect the Chinese, this may be reflected in death statistics.Methods Because the Chinese believe death is more likely during the ghost month, male and female deaths from all causes and from four common causes of death in the first and second fortnights of the seventh lunar months of 1995-2000 were compared in Hong Kong Chinese. Deaths in two consecutive fortnights 30 days before each year's seventh lunar month were used as controls. Death data were compared using the binomial test with a null hypothesis probability of 0.5 between the first and second fortnights.Results There was no difference in male deaths between the first and second fortnights of the control and seventh lunar months. While there were no significant differences in female deaths during the control month periods, fewer women died overall in the first fortnight of the seventh lunar month (p=0.026).Conclusion To protect their family, the Chinese women postpone death until after the hungry ghosts have been fed and hopefully banished forever.

I read with much interest the article by Vogel et al. ([1][1]), who state that the cause for lymphopenia in severe infections has been hitherto unclear and, based on their findings, propose that highly pathogenic infectious agents such as influenza virus directly impede the development of

Abstract Background: Ethnic differences necessitate a need for local reference intervals (RI), but establishing these can be challenging in some cultures that are reluctant to donate blood. Frozen sera are an alternative, but results can be questionable. Between 1998 and 2001, we collected blood samples from 343 healthy pregnant Chinese women (5–41 weeks' gestation), and in 2001 published gestational RI for thyrotropin thyroid stimulating hormone (TSH), free thyroxine (FT4) and free triiodothyronine (FT3) using the ACS180, now obsolete. As a pilot to re-establishing RI, TSH, FT4 and FT3 were re-assayed in archived specimens using contemporary assays. Methods: Thirty archived specimens (–80°C) with ACS180 TSH concentrations ranging from 0.25 to 3.7 mIU/L were measured using the Roche E170, Advia Centaur and Architect i2000 TSH, FT4 and FT3 assays, along with 10 newer contemporary samples. Results were compared to the original, and examined in context of past and present methodological performances in an external quality assurance (EQA) program. Results: All contemporary assays detected significantly lower TSH and increased FT4 and FT3 concentrations in the stored samples. Conclusions: With reference to methodological performances in EQA, the results obtained with contemporary assays suggest analyte deterioration in specimens and thus their unsuitability for re-establishing RI. Clin Chem Lab Med 2010;48:409–12.

INTRODUCTION Historical anecdotes suggest human beings can postpone death around important occasions. Some formal studies have claimed that elderly Jewish men and Chinese women in America postponed death around the Passover and Harvest Moon (or Mid-Autumn) Festival (HMF), respectively. METHODS We examined deaths from cancer, cerebrovascular and heart diseases in the Chinese around four important holidays celebrated in Hong Kong. From computerised data in 1995-2000, the expected weekly deaths for 12 weeks before and after Lunar New Year, Ching Ming, HMF and Chung Yeung holidays were calculated using a polynomial regression model for the three diseases in men and women, under and over the age of 75 years. The differences in the observed deaths one week before and one week after the four holidays were tested by the binomial test. RESULTS There were significantly fewer deaths overall in men before the holidays than after (p-value equals 0.0081), with most of the difference being due to cancer deaths, particularly among men over 75 years of age. For women, there were actually more deaths before than after the holidays. The data, stratified according to age, gender, disease and holiday, yielded only five out of 48 variables with a p-value of less than 0.05, which was slightly above chance, considering the large number of comparisons made. In four of the five situations, there were significantly fewer deaths before than after the holidays; but after Bonferroni correction, only the finding of fewer cancer deaths for men aged over 75 years before HMF was significant. CONCLUSION Other than cancer deaths in males, we found little evidence in this dataset of death postponement until after important holidays in the Hong Kong Chinese population.

High altitude inhabitants (HAI) are generally smaller than low altitude inhabitants (LAI). This anthropological observation has recently been confirmed in the Tibetan refugees who have settled in India since 1950s. Those settled at lower altitudes (970 m) are taller and muscular than compatriots settled at higher altitudes (3500 m). While lower socioeconomic status is implicated in growth retardation at higher altitudes, the smaller stature in adults in well-off communities says otherwise. Hypobaric hypoxia (HH) is the main challenge at high altitudes, which the long established HAI have overcome via biological adaptations, including larger chests, raised blood hemoglobin, and producing more nitric oxide (NO), which deliver similar levels of oxygen to tissues, as LAI. The Tibetans produce 10-fold more NO than LAI. NO is a potent inhibitor of steroidogenesis. Therefore I hypothesize that the short stature and lower musculature in HAI results from steroid deficiency precipitated by NO, which HAI produce to cope with HH.

Severe Acute Respiratory Syndrome (SARS) outbreak in 2002-03 caused morbidity in over 8000 individuals and mortality in 744 in 29 countries. Lymphopenia along with neutrophilia was a feature of SARS, as it is in respiratory syncytial virus (RSV) and Ebola infections, to name a few. Direct infestation of lymphocytes, neutrophils and macrophages by SARS coronavirus (CoV) has been debated as a cause of lymphopenia, but there is no convincing data. Lymphopenia can be caused by glucocorticoids, and thus any debilitating condition has the potential to induce lymphopenia via stress mechanism involving the hypothalamic-pituitary-adrenal axis. Cortisol levels are elevated in patients with RSV and Ebola, and cortisol was higher in SARS patients with lymphopenia before any steroid therapy. Glucocorticoids also down-regulate the production of proinflammatory lymphokines. Because of the insidious presentation, SARS was treated with antibacterial, antiviral and supra-physiological doses of glucocorticoids. Treatment with glucocorticoids complicated the issue regarding lymphopenia, and certainly calls into question the status of lymphokines and their prognostic implications in SARS.

Nitric oxide (NO) supposedly derived via l-arginine–NO synthase (NOS) pathway has been implicated in inhibiting steroidogenesis by binding the heme moiety of steroidogenic enzymes. Previously, nitrite, and to a lesser extent nitrate ions inhibited steroidogenesis via NO by hitherto unknown reduction mechanism. Recently, a putative mammalian nitrite reductase activity ascribed to complex III of mitochondrial respiratory chain complexes (MRCC) has been reported, where MRCC inhibitors reduced NO production from nitrite variably. We thus studied the effects of MRCC inhibitors on testosterone production in mouse Leydig tumor cells (MLTC-1) without (basal) or with human chorionic gonadotropin (hCG) stimulation. In stimulated MLTC-1, MRCC inhibitors decreased testosterone production, order being: complex III (antimycin A and myxothiazol) > complex I (rotenone) > complex II (thenoyltrifluoroacetone), while cAMP production increased inversely. In unstimulated MLTC-1, MRCC inhibitors in same order, increased basal testosterone production, which correlated inversely with the percentage inhibition of NO production, with one exception; while antimycin A did not inhibit NO production in the nitrite reductase study mentioned above, it increased basal testosterone production in the present study. While MLTC-1 expressed mRNA for endothelial and neuronal, but not inducible NOS, various stimulators and inhibitors of l-arginine–NOS pathway had no effect on basal testosterone production in MLTC-1 or fresh Balb/c Leydig cells. Moreover, hCG increased nitrate uptake into MLTC-1, which suggests the gonadotropin aids nitrite and nitrate ions in their steroidogenesis inhibitory activity. In conclusion, this study supports the existence of a surrogate mammalian nitrite reductase and the dormancy of l-arginine–NOS pathway in MLTC-1.

Autoimmune thyroid diseases (AITD) comprising Hashimoto's thyroiditis, primary myxedema, and Graves' disease are associated with autoantibodies directed against thyroglobulin and thyroid peroxidase (anti-TPO). Anti-TPO occur in 10% of pregnant women, half of whom reportedly develop postpartum thyroid dysfunction. We recently published data on the thyroid function reference ranges in pregnant Chinese but the AITD status of our cohort was unknown. In view of this missing information we have measured anti-TPO in specimens from our cohort stored at -80 degrees C, and compared these to those of patients with hyperemesis gravidarum (HG) and nonpregnant controls. After eliminating 3 outliers from 47 nonpregnant controls, the anti-TPO concentration range was 2.2-14.7 kIU/L (n = 44). In 282 pregnant control subjects, the anti-TPO levels were less than 14.7 kIU/L (upper limit of nonpregnant controls) in 189 (67%); between 14.7-55 kIU/L in 82 (29.1%); and greater than 55 kIU/L in 11 (3.9%). The percentage of women with anti-TPO greater than 14.7 kIU/L during the first, second, and third trimesters were 47% (30/64), 39% (49/126), and 16% (15/92), respectively. Anti-TPO level was significantly higher in pregnant controls compared to nonpregnant controls and patients with HG. With reference to other studies in which anti-TPO levels greater than 60 kIU/L were considered pathologic, we conclude that more than 96% of our pregnant controls were without AITD and the data on thyroid function reference ranges we previously reported remain valid.

Glucocorticoid treatment of patients with SARS: implications for mechanisms of immunopathology

Conversion of cholesterol to biologically active steroids is a multi-step enzymatic process. Along with some important enzymes, like cholesterol side-chain cleavage enzyme (P450scc) and 3beta-hydroxysteroid dehydrogenase/isomerase (3beta-HSD), several proteins play key role in steroidogenesis. The role of steroidogenic acute regulatory (StAR) protein is well established. A novel protein, BRE, found mainly in brain, adrenals and gonads, was highly expressed in hyperplastic rat adrenals with impaired steroidogenesis, suggesting its regulation by pituitary hormones. To further elucidate its role in steroidogenic tissues, mouse Leydig tumor cells (mLTC-1) were transfected with BRE antisense probes. Morphologically the BRE antisense cells exhibited large cytoplasmic lipid droplets and failed to shrink in response to human chorionic gonadotropin. Although cAMP production, along with StAR and P450scc mRNA expression, was unaffected in BRE antisense clones, progesterone and testosterone yields were significantly decreased, while pregnenolone was increased in response to human chorionic gonadotropin stimulation or in the presence of 22(R)OH-cholesterol. Furthermore, whereas exogenous progesterone was readily converted to testosterone, pregnenolone was not, suggesting impairment of pregnenolone-to-progesterone conversion, a step metabolized by 3beta-HSD. That steroidogenesis was compromised at the 3beta-HSD step was further confirmed by the reduced expression of 3beta-HSD type I (3ss-HSDI) mRNA in BRE antisense cells compared with controls. Our results suggest that BRE influences steroidogenesis through its effects on 3beta-HSD action, probably affecting its transcription.

In 1992, apparent digoxin concentrations determined by the Abbott TDx II assay 5 hours after the ingestion of 10 pills of traditional Chinese medicine containing toad secretions (chan su) by 7 volunteers, yielded results that were equimolar to bufalin measured by 2 in-house bufalin radioimmunoassays (RIAs). Recently, a 17-year-old Chinese female unintentionally took 100 (instead of 10) of these pills for a sore throat but suffered no ill effects. The blood bufalin concentration at 3 hours by 1 of the 2 RIAs was 10.93 nmol/L, which was commensurate with the dose. However, the apparent digoxin measured by a TDx II assay produced in 2004 was only 3.08 nmol/L, which probably reflects the change in the specificity of the polyclonal digoxin antisera used in the assay over the years. In 1989, the TDx assay was commended for its ability to detect poisoning from plant and animal cardenolides, a property that seems to be waning and, thus, bad news for those wishing to use the assay to detect alternative cardenolides. But, on the other hand, it possibly eliminates the “specter” of digoxin-like immunoreactive substance (DLIS) that has afflicted some digoxin assays, which can only be good news.

High altitude illness (HAI) affects 42% of individuals climbing above 3000 m. The pathophysiology of HAI, including water retention remains unclear. Although decreased nitric oxide (NO) production is implicated in the pathophysiology, a recent study reported increased NO in breathes of high altitude inhabitants, apparently produced to combat the high altitude hypoxia. NO binds heme generally and impairs cytochrome P450 steroidogenic enzymes. A consequence of increased NO production may be decreased steroidogenesis. An acute cortisol deficiency may thus be the reason for water retention and oedema, and explains why dexamethasone is effective in treating some aspects of HAI.

European Journal of Clinical InvestigationVolume 34, Issue 5 p. 382-384 Lymphopenia and neutrophilia in SARS are related to the prevailing serum cortisol N. S. Panesar, Corresponding Author N. S. Panesar The Chinese University of Hong Kong and Prince of Wales Hospital, Shatin, New Territories, Hong KongDr Nirmal S. Panesar, Department of Chemical Pathology, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, New Territories, Hong Kong, Special Administrative Region, China. Tel.: (852) 2632 2333; fax: (852) 2636 5090; e-mail: [email protected]Search for more papers by this authorC. W. K. Lam, C. W. K. Lam The Chinese University of Hong Kong and Prince of Wales Hospital, Shatin, New Territories, Hong KongSearch for more papers by this authorM. H. M. Chan, M. H. M. Chan The Chinese University of Hong Kong and Prince of Wales Hospital, Shatin, New Territories, Hong KongSearch for more papers by this authorC. K. Wong, C. K. Wong The Chinese University of Hong Kong and Prince of Wales Hospital, Shatin, New Territories, Hong KongSearch for more papers by this authorJ. J. Y. Sung, J. J. Y. Sung The Chinese University of Hong Kong and Prince of Wales Hospital, Shatin, New Territories, Hong KongSearch for more papers by this author N. S. Panesar, Corresponding Author N. S. Panesar The Chinese University of Hong Kong and Prince of Wales Hospital, Shatin, New Territories, Hong KongDr Nirmal S. Panesar, Department of Chemical Pathology, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, New Territories, Hong Kong, Special Administrative Region, China. Tel.: (852) 2632 2333; fax: (852) 2636 5090; e-mail: [email protected]Search for more papers by this authorC. W. K. Lam, C. W. K. Lam The Chinese University of Hong Kong and Prince of Wales Hospital, Shatin, New Territories, Hong KongSearch for more papers by this authorM. H. M. Chan, M. H. M. Chan The Chinese University of Hong Kong and Prince of Wales Hospital, Shatin, New Territories, Hong KongSearch for more papers by this authorC. K. Wong, C. K. Wong The Chinese University of Hong Kong and Prince of Wales Hospital, Shatin, New Territories, Hong KongSearch for more papers by this authorJ. J. Y. Sung, J. J. Y. Sung The Chinese University of Hong Kong and Prince of Wales Hospital, Shatin, New Territories, Hong KongSearch for more papers by this author First published: 17 May 2004 https://doi.org/10.1111/j.1365-2362.2004.01347.xCitations: 25Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Citing Literature Volume34, Issue5May 2004Pages 382-384 RelatedInformation

Low temperatures slow down metabolism, partly because the kinetic energy of molecules is reduced and enzymes may be structurally impaired. We now report that relative to its maximal activity at 37°C, adenylate cyclase (AC) still retained 25% functionality (determined as cyclic adenosine monophosphate [cAMP] production) at 4°C in mouse Leydig tumor cells (MLTC-1) in response to 50 IU/L human chorionic gonadotropin (hCG), whereas steroidogenic acute regulatory (StAR) protein mRNA and testosterone production were completely impaired. The incubation of MLTC-1 with the phosphodiesterase inhibitor (3-isobutyl-1-methylxanthine; IBMX) resulted in significantly increased intracellular cAMP concentration at all 3 temperatures, but this had no impact on testosterone production. AC, cAMP, and phosphodiesterase form an important intracellular second-messenger mechanism in many organisms, some that inhabit very low temperature niches. The cold-resistance of AC and phosphodiesterase may thus have evolved to cope with adverse conditions. Although hibernation may lead to decreased steroid hormone production, it is also likely that cold-mediated decreased steroid hormone production induces hibernation.

The mouse Leydig tumor cells (MLTC-1) were derived from a transplantable Leydig cell tumor carried in C57BL/6 mice. The original cell line (M5480) produced testosterone and little progesterone. However, it was later shown that there were two subtypes of the cell line, one producing mainly progesterone and termed M5480P and the other which produced androgens and termed M5480A. MLTC-1 cells are reportedly derived from the former. We studied the production of testosterone by MLTC-1 cells using a specific and sensitive testosterone RIA, tandem mass spectrometry (TMS) and examined the expression of mRNA of some key enzymes involved in steroidogenesis. Although the molar yields were 1:20:60 for testosterone, androstenedione and progesterone, respectively, in response to human chorionic gonadotropin (hCG), testosterone measured by our RIA accounted for 94% of the testosterone immunoreactivity. Both MLTC-1 and Balb/c Leydig cells expressed Steroidogenic Acute Response (StAR) protein mRNA in response to hCG. Cytochrome P450 17alpha-hydroxylase/17,20-lyase mRNA was expressed constitutively in MLTC-1 and Balb/c Leydig cells. Whereas the latter expressed 17beta-hydroxydehydrogenase/17-ketoreductase isoform Type 3mRNA in response to hCG, MLTC-1 cells expressed isoform Type 7 constitutively. The absence of isoform Type 3 in MLTC-1 cells thus may account for the low conversion of androstenedione to testosterone in this cell line. However, with a very specific and sensitive RIA even the low production of testosterone becomes meaningful. In conclusion MLTC-1 cells produce testosterone.