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Biomedical subjects

K Tan

Publications and source records attributed to K Tan.

At least 73 records · Page 4Linked to original sources

An enzyme-linked immunoadsorbent assay for human pituitary glycoprotein free alpha-subunit: evaluation and initial experience in patients with pituitary disease.

An enzyme-linked immunoadsorbent assay (ELISA) for measuring human pituitary glycoprotein free alpha-subunit is described. Pituitary tumours may secrete glycoprotein hormones, their free subunits (alpha, beta) or a combination of these. Non-functioning adenomas often secrete free alpha-subunit. Assays for free alpha-subunit have previously used radioimmunoassay or immunoradiometric principles. Some of these methods are time-consuming and lack specificity and sensitivity. In order to overcome these problems, we have developed a two-site ELISA for alpha-subunit which uses a monoclonal antibody to alpha-subunit as the capture antibody to provide greater specificity. An affinity-purified polyclonal anti alpha-subunit conjugated to alkaline phosphatase was the signal antibody. Detection and quantification were based on phenolphthalein monophosphate conversion to phenolphthalein. The ELISA specifically measured glycoprotein free alpha-subunit in serum or plasma, discriminating between alpha-subunit and the intact glycoprotein hormones. The assay can be completed in 4 h. The assay sensitivity was 0.03 micrograms/l, and a normal range of 0.05 to 0.22 micrograms/l was established. In a retrospective study, elevated circulating glycoprotein alpha-subunit was detected in 22% of patients with non-functioning pituitary tumours previously treated with surgery and/or radiotherapy.

Adolescent↗

Studying brain development with quail-chick neural chimeras.

Avian embryonic neural chimeras are constructed by substituting defined areas of the neural epithelium of a chick embryo by their exact counterpart obtained from a quail embryo at the same developmental stage. The experiment can also be performed using the quail as a host and the chick as a graft donor. The stages elected are either the late neurula (0 to 3 somites) or the stage after cephalic vesicles formation (10 to 14 somites) but in all cases before the onset of vascularization of the neural primordium. Quail and chick territories can be recognized in the chimeras any time after the graft owing to the particular structure of the quail nucleus or by means of species-specific antibodies. Quail-chick chimeras have been instrumental in the study of the ontogeny of the medulla oblongata and of the cerebellum. The complex morphogenetic movements and cell migrations which occur during the development of this part of the brain have been worked out by this method. The main results obtained are described in the article.

Animals↗

Which calcium channel blocker for ischaemic heart disease?

Calcium channel blockers have been available since the early 1960s. Extensive research has been undertaken to evaluate their usefulness in the treatment of patients with ischaemic heart disease. We have reviewed the pharmacology of these drugs and the major clinical trials. In particular, we have examined the effect of calcium channel blockers on the progression of atheroma, and their role in the following clinical settings: following myocardial infarction, following non-Q-wave myocardial infarction, and in unstable angina.

Angina, Unstable↗

Development of the nuclei and cell migration in the medulla oblongata. Application of the quail-chick chimera system.

We have tried to obtain new insight into the development of the medulla oblongata by using the quail-to-chick chimera system. Five types of isotopic and isochronic grafts were carried out, between quail and chick embryos, at the 10- to 12-somite stage: exchanges of (I) the entire myelencephalon, (II) the dorsal half of the myelencephalon, (III) the ventral half of the myelencephalon, (IV) the right half of the myelencephalon and (V) the dorsal quarter of the myelencephalon. Before analyzing the chimeric embryos, we studied the ontogeny of the various nuclei in the medulla oblongata of normal birds. The first appearance of nuclei in quail embryos preceded in many cases that of their chick counterpart by 12 to 24 h. The adult pattern of the nuclei was established by E8 in quail and E9 in chick. Similarly, during early development of chimeras, the migration of quail cells began earlier than that of chick cells. This shows that the species specific temporal sequence of proliferation and migration is not significantly altered by transplantation into the host. The possibility of grafting selectively the ventral or dorsal half of the neural tube allowed us to distinguish the fate of the cells belonging respectively to the alar and the basal plate. The nuclei with a total or partial motor function, such as the nucleus nervi abducentis, the nucleus nervi facialis, the nucleus nervi glossopharyngei and the nucleus motorius dorsalis nervi vagi, have either an exclusive or predominant origin from the basal plate. In contrast, the nuclei with essentially or exclusively sensory components (i.e., nucleus angularis, nucleus laminaris, nucleus magnocellularis) arise from the alar plate. The reticular formation such as the nucleus reticularis gigantocellularis and the nucleus reticularis subtrigeminalis was strikingly mixed, with both alar and basal plate origin of neurons. Active dorsoventral migrations of cells originating migrations from the dorsal neural tube, the "rhombic lip", contribute the ventral nuclei (i.e., nuclei pontis medialis, lateralis and olivaris inferior), whose functions are essentially associative. This study shows different types of cell migration. Dorsoventral and ventrodorsal movements are essentially active from E5 to E8. In the medulla oblongata, the dorsoventral stream is highly predominant. From E8 to E9, cells belonging to the marginal stream cross the midline laterally in both directions. Beyond E12, longitudinal migrations occur ventrally in both rostrocaudal and caudorostral directions. The immunohistochemical analyses carried out on chimeras generated in experiment V revealed the existence of fibers in marginal zones prior to the onset of the migration of cell bodies.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

A review of forty-five years study of Hiroshima and Nagasaki atomic bomb survivors. Residual radioactivity in neutron-exposed objects and residual alpha radioactivity in black rain areas.

The residual Eu-142 radioactivity due to the atomic bomb explosion in 1945 was first found in 1976 by in-situ high resolution gamma-ray spectrometry at Hiroshima. Since then, various studies on this nuclide have continued not only in Hiroshima but also in Nagasaki and they have contributed to the reevaluation of the neutron dose due to the A-bombing. By radiochemical separation methods and alpha-ray spectrometry, rather high levels of plutonium were found in the surface soil and in the bottom sediment of water reservoir which were collected at "Black rain area" in Nagasaki. The U-234/U-238 activity ratios for the uranium leached with 0.1 HNO3 from the surface of soil samples were found to be relatively higher for the samples which were collected at "Black rain area" in Hiroshima.

Alpha Particles↗

Cross-correlation of cyclosporine concentrations and biochemical measures of kidney and liver function in heart and heart-lung transplant recipients.

Cross-correlation of cyclosporine concentrations with results of biochemical tests of renal and liver function, measured during the first three months post-operatively, was carried out retrospectively in 24 heart and eight heart-lung transplant recipients to assess the temporal relationship between cyclosporine treatment and the development of possible toxic side-effects. We found a statistically significant negative correlation (95% confidence interval of the mean correlation coefficient did not overlap zero) between the five-day mean concentration of cyclosporine in whole blood (but not plasma) as measured with nonselective (NSRIA) and selective radioimmunoassays (SRIA) and the mean reciprocal creatinine concentration measured in the subsequent five days. In 15 of 32 (47%) patients the negative correlation coefficient exceeded 0.7 (high susceptibility), whereas in 11 of 32 (34%) it was between 0.5 and 0.7 (medium susceptibility), and in only six of 32 (19%) was it less than 0.3 (low susceptibility). We found no consistent correlations between cyclosporine measurements and results of other renal-function tests or liver-function tests. This suggests that therapeutic doses of the drug are not hepatotoxic in most patients. There was, however, a significantly correlated decrease in the NSRIA/SRIA ratio and in serum bilirubin concentration with time post-operatively, reflecting improvement in hepatic function and clearance of the cyclosporine metabolites that are detected by NSRIA. Assays of cyclosporine in whole blood, but not in plasma, are of value in anticipating changes in renal function after heart and heart-lung transplantation.

Biomarkers↗

Avian spinal cord chimeras. Further studies on the neurological syndrome affecting the chimeras after birth.

These experiments bring new information concerning the immunological status after birth of quail----chick spinal cord chimeras. Such birds have been produced using recipient flocks of chickens different from those in our previous experiments. The breakdown of tolerance after hatching has been recorded and found to vary with the origin of the embryos. Chickens of broiler JA 657 strain and of a white leghorn strain raised in Japan started to exhibit signs of neural graft rejection later in life than the white leghorn chickens from a French breeder used in our previous studies. As previously described, in two animals, long-term tolerance was observed only for allogeneic chick----chick neural tube grafts. In one chimera the neurological syndrome resulting from rejection was reversible, and no signs of immune attack of the grafted central nervous tissue could be detected at sacrifice. This and other observations reported in this article strongly support the contention that the host immune response to foreign neural tissues starts in peripheral nerves and ganglia where no blood-brain barrier exists rather than in the spinal cord. A humoral response of the host against non-polymorphic quail antigens present on fibroblasts was observed in all birds at the time of rejection.

Animals↗

Reproductive hormones in menstrual blood.

Menstrual and peripheral blood samples were collected from 19 regularly cycling women on days 1-3 of the menstrual cycle. Menstrual samples were collected with a soft silicone rubber menstrual cup. Hematocrit, PRL, LH, FSH, estradiol (E2), and progesterone (P4) were measured in all samples. Validation studies were carried out for RIAs of PRL, LH, and FSH in menstrual plasma. The menstrual plasma PRL level was significantly higher than its peripheral blood level on day 1 (63.3 +/- 14.7 and 12.1 +/- 2.9 micrograms/L, respectively; t = 3.331; P less than 0.01), and menstrual PRL was significantly higher on day 1 than on day 2 (t = 3.340; P less than 0.01). There was a strong negative correlation between log menstrual PRL concentration and time of onset of menstruation (r = -0.596; P less than 0.01). Menstrual plasma FSH levels were significantly lower than peripheral levels on each of days 1-3 (day 1:t = 4.787; P less than 0.001), and there was a significant positive correlation between menstrual and peripheral levels (r = 0.607; P less than 0.01). By contrast, menstrual plasma LH was significantly higher than the peripheral level on days 1 and 2 (day 1:t = 3.105; day 2:t = 3.180; P less than 0.01), with no correlation between menstrual and peripheral levels. Menstrual E2 was slightly lower than and significantly positively correlated with peripheral E2 (r = 0.646; P less than 0.01). Menstrual P4 was lower than but showed no correlation with peripheral levels. As expected, the menstrual blood hematocrit was less than 0.20 and highly significantly lower than that of peripheral venous blood. These results suggest that PRL is released in substantial amounts from secretory endometrium into the menstrual flow during the first day of menstrual breakdown. LH may also be released in small amounts from menstrual endometrium, while menstrual FSH, E2, and P4 probably arise entirely from the peripheral circulation.

Adult↗

Detailed assessment of big big prolactin in women with hyperprolactinemia and normal ovarian function.

Six women with elevated circulating levels of big big PRL (BBPRL) and apparently normal ovarian function were variously studied through a menstrual cycle and menstruation, through pregnancy and suckling, and during stimulation tests with TRH and suppression with bromocriptine. No significant changes in monomeric PRL were demonstrated during the menstrual cycle, but all subjects showed a small and significant rise in BBPRL during the preovulatory phase. High PRL levels were present in day 1 menstrual plasma, but BBPRL was only present in low concentrations. All subjects (n = 5) demonstrated a rise in both PRL and BBPRL during pregnancy, with a consistent tendency for PRL to increase to a proportionately greater extent than BBPRL. One subject exhibited a rise in PRL (by 93%), but not BBPRL, 30 min after suckling. TRH caused a brisk rise in PRL (by 363 +/- 116%) but only a sluggish rise in BBPRL (by 17.5 +/- 7.4%; n = 3). Bromocriptine rapidly suppressed PRL (by 81.8 +/- 34.4%), but only slowly suppressed BBPRL (by 21.0 +/- 8.7% after 6 h; n = 3). Plasma binding studies did not demonstrate any evidence of a circulating specific PRL-binding protein. These data indicate that plasma concentrations of BBPRL may vary under the influence of a number of factors, but are much less sensitive to TRH stimulation, bromocriptine suppression, pregnancy, and suckling than PRL. The occurrence of BBPRL does not seem to be due to a specific circulating binding protein.

Adult↗

Teratological assessment of exposure to time-varying magnetic field.

A teratological assessment was performed using rats that were exposed to an alternating magnetic field. The magnetic field had a sawtooth waveform similar to that produced by video display terminals (VDTs). Female rats were exposed 2 weeks prior to and throughout pregnancy at a rate of 7 h/day. Three intensities of magnetic field (5.7, 23 or 66 microT) were used. All of these field intensities were much greater than those to which VDT users are exposed. A slight but statistically significant decrease in maternal lymphocyte count for the highest intensity field was found as compared with the control group. However, the lymphocyte count was within the normal range, and the observed changes in hematological parameters were considered mild. No other maternal or fetal parameters that were examined showed a significant difference for any of the three field intensities. Where minor variations in skeleton development were observed they were known to be the common "noise" that appears in every teratological evaluation.

Animals↗

Production of an ovine monoclonal antibody to testosterone by an interspecies fusion.

Hybridomas were made between NS1/1-Ag4-1 mouse myeloma cells and peripheral blood lymphocytes from a sheep immunized with a testosterone-protein conjugate. ELISAs were developed to detect ovine IgG and specific ovine anti-testosterone and these were used to screen the colonies. Although the cells fused acceptably only 3% of colonies secreted detectable quantities of antibody. The antibody was secreted at low levels (2.5 ng/ml) but was of high affinity (KD = 7.63 x 10(-12) M/1). One line, O/M 4.22, continued to secrete in culture for four months until the termination of the experiment.

Animals↗

Relationship of somatomedin-C/insulin-like growth factor I levels to conventional nutritional indices in critically ill patients.

Twenty ICU patients, with varying diagnoses and degrees of catabolism, were studied prospectively to determine whether somatomedin-C/insulin-like growth factor I (SMC/IGFI) is related to the conventional nutritional indices, plasma prealbumin, transferrin and albumin, and nitrogen balance (NB) in critical illness. Mean SMC/IGFI concentration in these critically ill patients was below the lower limit of the reference range. SMC/IGFI concentrations correlated with NB for the 24 h before measurement (r = .38, p less than .01) and with cumulative NB for the previous 2 (r = .50, p less than .01), 3 (r = .34, p less than .05), and 5 days (r = .46, p less than .05). Prealbumin correlated with cumulative 5-day NB (r = .39, p less than .05). Plasma albumin and transferrin concentrations did not correlate with NB for any of these time periods. SMC/IGFI concentrations correlated with cumulative protein (r = .59, p less than .01), carbohydrate (r = .63, p less than .01), and energy intake (r = .64, p less than .01). SMC/IGFI was the only index which consistently correlated with NB. We conclude it is a useful index of nutritional status in critically ill patients.

Adult↗

Serum insulin-like growth factor I levels in adult diabetic patients: the effect of age.

Despite reports of reduced serum insulin-like growth factor (IGF) levels in experimentally diabetic animals, human diabetic patients have been reported to have decreased, normal, or even elevated levels. This study was a cross-sectional examination of the effect of age on immunoreactive IGF-I levels in adult patients with insulin-dependent or noninsulin-dependent diabetes mellitus (IDDM and NIDDM) attending a diabetes out-patient clinic. The patients and normal subjects studied were divided into the age ranges 21-30, 31-40, 41-50, 51-60, and over 60 yr. For all ages combined, the mean IGF-I level (+/- SD) was 0.84 +/- 0.26 U/ml (202 +/- 62 ng/ml) in 133 normal subjects, significantly reduced to 0.41 +/- 0.17 U/ml in 121 IDDM patients, and 0.49 +/- 0.19 U/ml in 46 NIDDM patients (both P less than 0.001). In both groups there was a marked decline in IGF-I with increasing age (P less than 0.01). Except for NIDDM patients aged 21-30 yr (only two patients), IGF-I levels in both IDDM and NIDDM patients were significantly lower in every age range than those in age-matched normal subjects, but did not differ between the two diabetic groups. Glycosylated hemoglobin levels correlated inversely with IGF-I levels only in younger patients with IDDM (r = -0.486; P less than 0.05 for patients aged 21-40 yr). We conclude that factors common to IDDM and NIDDM, perhaps related to relative nutritional deficiency at the cellular level, cause a reduction in serum IGF-I levels, and that this reduction occurs independently of age-related changes in IGF-I.

Adult↗

Morphogenetic movement of the thyroid primordium in the rat: a scanning and transmission electron microscopic study.

This study deals with the fine structural and three dimensional aspects of the early morphogenetic movements of the thyroid primordium in rat embryos. By scanning electron microscopy, the cells of the presumptive thyroid area show peculiar cauliflower-like structures at day 10 of gestation prior to the starting of its invagination. These structures increase in number as the invagination proceeds. Each cauliflower-like structure consists of a large apical cytoplasmic process with many microvilli and a few small bleb-like protrusions. This phenomenon is then followed by the decrease and ultimate disappearance of the microvilli and bleb-like protrusions, while many large spherical bodies, possibly derived from the bleb-like protrusions and cell debris, appear on the epithelium of the thyroid primordium, especially around the marginal zone of the primordial invagination which soon closes. These observations suggest that the gross morphogenetic movement of the thyroid primordium is due partly to the changes of cell shapes in this area. Transmission electron microscopy reveals conspicuous bundles of microfilaments about 6 nm in diameter located in the apical cytoplasm and converging on well-developed junctional complexes during the invagination process. The appearance of the cytoplasmic processes and bleb-like protrusions appearing in the cells of this region is believed to indicate a role in the invagination of the thyroid primordium and the closure of the starting point of the invagination.

Actin Cytoskeleton↗