Biomedical subjects

Nirmal S Panesar

Publications and source records attributed to Nirmal S Panesar.

8 recordsLinked to original sources

PubMed2005

Chloride efflux in unstimulated Leydig cells causes autonomous cAMP production and stimulatory/inhibitory steroidogenesis with an efflux inhibitor.

Gonadotropins cause immediate chloride secretion in Leydig cells, which still have an unknown physiological. Thyroid and Leydig cells produce more cAMP and steroids, respectively, under low or chloride-free conditions. Here, we show that chloride efflux mediated by incubation of Mouse Leydig Tumor cells (MLTC-1) in hypotonic or chloride-free isotonic buffers results in more cAMP production without any gonadotropic stimulation. MLTC-1 cells incubated with 0.5mM diphenylamine-2-carboxylate (DPC), a chloride efflux inhibitor, produced increased amounts of testosterone as chloride ions were substituted by gluconate or sulphate ions under isotonic conditions. There was also an up-regulation of steroidogenic acute regulatory protein and 3beta-hydroxysteroid dehydrogenase/isomerase type I mRNAs, without human chorionic gonadotropin. With the exception of cAMP production, 2mM DPC inhibited all of the above, including the transcription of constitutively expressed cholesterol side-chain cleavage enzyme and the L19 house-keeping gene. Although it was speculated that gonadotropin mediated chloride secretion could aid steroid hormone release, we conclude that the real reason for chloride secretion in Leydig cells may be to "kick start" cAMP production.

Animals↗

PubMed2005

Changing characteristics of the TDx digoxin II assay in detecting bufadienolides in a traditional Chinese medicine: for better or worse?

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.

Adolescent↗

PubMed2004

High altitude sickness. Is acute cortisol deficiency involved in its pathophysiology?

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.

Altitude Sickness↗

PubMed2003

Lymphopenia in SARS.

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Adrenocorticotropic Hormone↗

PubMed2003

mRNA of placental origin is readily detectable in maternal plasma.

The discovery of circulating fetal nucleic acid in maternal plasma has opened up new possibilities for noninvasive prenatal diagnosis. Thus far, a gender- and polymorphism-independent fetal-specific target that can be used for prenatal screening and monitoring in all pregnant women has not been reported. In addition, the origin of such circulating nucleic acid has remained unclear. Here we provide direct evidence that the placenta is an important source of fetal nucleic acid release into maternal plasma by demonstrating that mRNA transcripts from placenta-expressed genes are readily detectable in maternal plasma. The surprising stability of such placental mRNA species in maternal plasma and their rapid clearance after delivery demonstrate that such circulating mRNA molecules are practical markers for clinical use. The measurement of such plasma mRNA markers has provided a gender-independent approach for noninvasive prenatal gene expression profiling and has opened up numerous research and diagnostic possibilities.

Base Sequence↗

PubMed2003

Mouse Leydig tumor cells produce C-19 steroids, including testosterone.

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.

17-Hydroxysteroid Dehydrogenases↗

PubMed2003

The concentration of circulating corticotropin-releasing hormone mRNA in maternal plasma is increased in preeclampsia.

BACKGROUND: Increased fetal DNA in maternal plasma/serum has been reported in pregnancies complicated by preeclampsia. We hypothesize that fetal RNA may also be increased in maternal plasma in preeclampsia. METHODS: We developed a real-time quantitative reverse transcription-PCR assay to measure the concentration of the mRNA of the corticotropin-releasing hormone (CRH) locus. Peripheral blood samples were obtained from healthy pregnant women both before and 2 h after delivery. Peripheral blood samples were also obtained from women suffering from preeclampsia and controls matched for gestational age. Plasma was harvested from these samples, and RNA was extracted. Plasma RNA was subjected to analysis by the reverse transcription-PCR assay. RESULTS: CRH mRNA was detected in the plasma of 10 healthy pregnant women in the third trimester. CRH mRNA was found to be cleared very rapidly after cesarean section, with no detectable signal by 2 h postpartum. Plasma CRH mRNA concentrations were 1070 and 102 copies/mL, respectively, in 12 preeclamptic women and 10 healthy pregnant women matched for gestational age (Mann-Whitney test, P <0.001). CONCLUSION: Plasma CRH mRNA represents a new molecular marker for preeclampsia. Maternal plasma RNA is gender- and polymorphism-independent and may allow noninvasive gene-expression profiling of an unborn fetus.

Blood Circulation↗

PubMedDate not supplied

Is four a deadly number for the Chinese?

BACKGROUND: The numbers 4, 14 and 24 are associated with death for Cantonese-speaking Chinese people, as the words for these numbers sound like the words for "death", "must die" and "easy to die", respectively. A previous study in the United States investigating psychological stress engendered by fear of the number 4 found more cardiac deaths in Chinese and Japanese people, compared with white Americans, on the 4th day of the month. OBJECTIVE: To determine whether more cardiac deaths occur in Hong Kong Chinese people on the days of the month with "deathly connotations" (4, 14 and 24). DESIGN: Analysis of mortality data (1995-2000) of the Chinese population of Hong Kong from the Census and Statistics Department of the Hong Kong Government for these three days of the month, compared with the remaining days, according to both the Gregorian and Lunar calendars. RESULTS: There were 17 346 cardiac deaths registered under ICD-9 codes 410-414 in 1995-2000. The mean (+ 1 SD) of the cumulative number of cardiac deaths on each day of the month was 587 (+ 30) for the Gregorian calendar or 573 (+ 24) for the Lunar calendar. The mean number of deaths on the 4th, 14th and 24th day of the month was not significantly different from the mean number of deaths on the remaining days of the month. CONCLUSION: Our study of Hong Kong Chinese people does not support the concept that more cardiac deaths occur in Cantonese people on the 4th, 14th and 24th day of the month.

Cause of Death↗