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Biomedical subjects

M S Lin

Publications and source records attributed to M S Lin.

At least 127 records · Page 7Linked to original sources
PubMed1982

Evidence that sister chromatid exchanges and chromatid breaks are two independent events.

The relative frequencies of sister chromatid exchanges (SCE) and chromatid breaks in BrdU (5-bromodeoxyuridine) - sensitive site (lq22 leads to lq23) in Chinese hamster cells after BrdU incorporation were studied. The results show that chromatid breaks do not follow the "exchange hypothesis" and provide evidence that chromatid breaks and SCEs are two independent events despite some common features.

Animals↗
PubMed1982

Partial reversal of radiation-induced immunosuppression by T-lymphocyte lysate.

BN rats were irradiated with 500 rad of 60Co 1 day before immunization with 0.1 mg of ovalbumin in alum hydroxide gel. The onset of reaginic and haemagglutinating antibody synthesis was suppressed to a non-detectable level for at least 3-4 weeks. When these irradiated rats were injected intraperitoneally with 10(8) viable or sonicated thymocytes 1 day after irradiation, the suppressed reaginic and haemagglutinating antibody synthesis was successfully restored. This suggests that: (i) thymocytes can restore the radiation-induced immunosuppression, but viability of thymocytes is not essential in this immune restoration; (ii) active biological molecules exist in the cytoplasmic pool of the normal thymocytes which can restore the radiation-induced immunosuppression; and (iii) the thymus not only plays a central role in the normal morphological development of the lymphoid system and its functional immunological maturation, but may also play an important role in the reversal of radiation-induced immunosuppression. To investigate tissue specificity of the factors that are actively engaged in the restoration of the suppressed immune response, peripheral lymphocytes, spleen cells, bone marrow cells and kidney cells were also tested. The results demonstrated that both peripheral lymphocytes and spleen cells could restore the suppressed immune response, but not bone marrow cells or kidney cells. This suggests that the active factors may be present only in T lymphocytes. Since the active factors could be found in the tissues other than thymocytes and non-stimulated lymphocytes, they appear to be different from thymosin, transfer factor or lymphokines derived from sensitized lymphocytes, and they were most likely not synthesized de novo.

Animals↗
PubMed1981

Variability of plasma hydralazine concentrations in male hypertensive patients.

The efficacy and toxicity of hydralazine differ widely among individual patients, possibly because of different sensitivities to drug effect or as a reflection of pharmacokinetic differences. Therefore, the variability in plasma hydralazine concentrations after single intravenous and single and multiple oral doses was studied in 9 male hypertensive patients. After an intravenous dose of 0.3 mg/kg the area under the plasma concentration time curve (AUC) varied over less than a twofold range 17.5-29.5 muM-minute. However, after a single oral dose, 1 mg/kg, and after at least the fifth dose of a regimen consisting of 1 mg/kg given every 12 hours, there were much wider variations in AUC values: 4.0-30.4 and 3.2-38.5 muM-minute, respectively. Similar ranges in peak hydralazine concentration, Cp, were also noted, 0.12-1.31 muM after single oral dose and 0.10-1.39 muM after the multiple dose regimen. A significant portion of the observed interpatient variability could be explained by differences in acetylation ability. The AUC and Cp values for both the single and multiple oral doses were significantly lower (P less than 0.001) in rapid than in slow acetylators. Therefore, determining the acetylation ability of patients requiring hydralazine may help to optimize therapeutic benefit and minimize toxicity.

Acetylation↗
PubMed1981

Determinants of response to intravenous hydralazine in hypertension.

There is marked interindividual variation in hypotensive response to intravenous hydralazine (H). We examined the determinants of response in patients with hypertension. After a single intravenous dose of 0.3 mg/kg H, response was correlated independently (r = 0.8364) with both predrug blood pressure and acetylator index (AI). Intravenous dose ranging studies showed that response also depended on the amount of H in the systemic circulation. Although plasma H levels depend on AI after oral doses, this is not so after intravenous administration. AI must therefore affect response to H by an alternative, presumably nonmetabolic mechanism which, not related to AI, perhaps indicating specificity of this effect for H. These data reinforce the potential usefulness of determining AI before giving H to a patient.

Acetylation↗
PubMed1981

Plasma noradrenaline as a measure of baroreflex sensitivity in hypertensive man.

1. Changes in plasma noradrenaline levels and heart rate were used as measures of baroreflex sensitivity in six hypertensive subjects given serial incremental doses of sodium nitroprusside (intravenously) to lower blood pressure. 2. The rises in both heart rate and plasma noradrenaline concentration were linearly related to the decrement in blood pressure and inversely related to the severity of the hypertension. 3. A positive correlation between rise in heart rate and rise in plasma noradrenaline was found for each subject. With increasing severity of hypertension, a greater increase in heart rate occurred for each increment in plasma noradrenaline concentration. 4. Baroreflex sensitivity can be assessed by relating changes in heart rate to change in arterial pressure; however, this method does not distinguish the relative contributions of the vagal and sympathetic components of the autonomic neural response or variations in the chronotropic response to sympathetic stimulation. 5. Changes in plasma noradrenaline levels in response to graded reductions in blood pressure may be a more appropriate measure of baroreflex sensitivity than the methods currently used in clinical investigation.

Heart Rate↗
PubMed1981

Diploid-triploid mixoploidy: clinical and cytogenetic aspects.

A patient with 46, XY/69,XXY mixoploidy (a mixture of cell populations whose component cells differ in their chromosome numbers, irrespective of whether these numbers are euploid or aneuploid) who had some clinical manifestations of the Russell-Silver syndrome is reported. Triploidy results in a clinically recognizable lethal syndrome with hydatidiform placental changes, severe intrauterine growth deficiency, dysplastic cranial bones, eye defects, cleft lip and/or, palate malformed ears, micrognathia, syndactyly, genital anomalies and, rarely, spina bifida. Less severe are instances of diploid-triploid mixoploidy and patients are more likely to survive; one of these patients was detected at birth because of asymmetric growth deficiency with syndactyly. Cytogenetic and flow cytometric studies demonstrated absence of triploid cells in peripheral lymphocytes while varying proportions of triploid cells were found in fibroblast cultures derived from each limb. The triploid cell population disappeared with prolonged cell culture. Replication studies with 5-bromodeoxyuridine-DAPI fluorescence revealed two active X chromosomes, and marker chromosomes suggested a paternal origin for the extra haploid set. The following points are emphasized: (1) diploid-triploid mixoploidy can be suspected clinically; (2) the triploid cell population may not be detectable on examination of peripheral blood (3) the relative degree of asymmetry in the growth deficiency does not appear to relate to the proportion of triploid cells; and (4) both X chromosomes may remain active in the presence of an extra haploid set of chromosomes.

Abnormalities, Multiple↗
PubMed1981

Local colloid trapping in the liver in the inferior vena cava syndrome.

Local radioactive areas in the liver were observed as a result of superficial cavoportal shunting of radiocolloids in two patients with the inferior vena cava syndrome. In one patient a paraumbilical and/or a recanalized umbilical vein was apparently involved in the hepatopetal shunting. In the other patient a superficial anastomosis other than the paraumbilical vein shunted colloid to the liver. Relatively discrete areas of increased radioactivity, single or multiple, were seen in the left lobe. Virtually all reported instances of hepatopetal shunting of radioparticles in a superior or an inferior vena cava syndrome have demonstrated similar findings. Various hepatopetal collateral pathways in infrarenal caval obstruction are considered, and factors that could affect liver scan findings in the infrarenal obstruction are discussed.

Collateral Circulation↗
PubMed1980

Chromosome fragility and susceptibility of Bloom's syndrome fibroblasts to SV40 transformation.

A comparison of the frequencies of chromosomal aberrations and the rates of SV40 transformation was made using fibroblasts obtained from 2 patients with Bloom's syndrome (BS) and from a normal individual. BS cells were found to be more susceptible to chromosome damage, in confirmation of earlier reports, but surprisingly, BS cells were distinctly less prone to transformation.

Cell Transformation, Viral↗
PubMed1980

Hydralazine kinetics in hypertensive patients after intravenous administration.

Previous studies on intravenous hydralazine kinetics have been performed using nonselective analytical techniques that measure not only hydralazine but also certain hydralazine metabolites such as hydralazine pyruvic acid hydrazone (HPH). We studied the time course of hydralazine and HPH in eight hypertensive patients after 0.3 mg/kg intravenous with selective high-pressure liquid chromatographic assays. "Apparent" hydralazine concentrations were also determined using a nonselective gas-liquid chromatographic procedure. Total plasma clearance, CLT[72.9 +/- 4.9 (SEM) ml . min-1 . kg-1], apparent volume of distribution, Vd area (5.83 +/- 0.30 1 . kg-1), steady-state volume of distribution, Vd ss (1.83 +/- 0.17 . kg-1), and terminal half-life, t1/2 (53.7 min, harmonic mean) were independent of acetylator phenotype. The high ClT is compatible with rapid intravascular conversion of hydralazine to HPH and a high hepatic extraction ratio. Peak HPH concentrations occurred 10 to 60 min after dose; mean HPH t1/2 was 239 min. "Apparent" hydralazine concentrations were usually highest in the 2-min plasma sample and declined with a mean t1/2 of 296 min. Reports based on nonselective assay methods have underestimated CLT, Vd ss, and Vd area and have overestimated the t1/2 of hydralazine.

Half-Life↗
PubMed1980

Hydralazine kinetics after single and repeated oral doses.

In reports on hydralazine kinetics plasma hydralazine levels have been measured with nonspecific assay techniques. The techniques used also include acid-labile hydralazine metabolites and therefore markedly overestimate hydralazine levels. We have developed specific, sensitive assay methods for the measurement of hydralazine and its major plasma metabolite, hydralazine pyruvic acid hydrazone (HPH). By these methods, we determined hydralazine and HPH kinetics after single and repeated oral doses of hydralazine in eight hypertensive patients. Hydralazine bioavailability in the fast acetylator group (9.5% single dose, 6.6% repeated doses) and in the slow acetylator group (31.3% single dose, 39.3% repeated doses) was phenotype dependent. Peak plasma levels were lower than those reported with nonspecific assays: 0.32 microM for the single dose and 0.14 microM for repeated doses in the fast acetylator group and 1.03 microM for the single dose and 0.96 microM repeated doses in the slow acetylator group. There was no alteration in kinetics and no cumulation in plasma on repeated administration. HPH plasma levels were proportional to those of hydralazine in both acetylator groups and were 2.5 to 4 times as high as those of hydralazine. Elimination half-lifes were phenotype independent, ranging from 4 to 6 hr. HPH cumulated in the rapid but not in the slow acetylator group after repeated doses of hydralazine.

Acetylation↗
PubMed1980

Thyroid hypofunction in spinal cord injury patients.

Our experience in the screening and detection of hypothyroidism in 225 spinal injury patients is described. Clinical features compatible with hypothyroidism are frequently encountered in these patients and require thyroid function testing to exclude or confirm thyroid hypofunction. Two cases of hypothyroidism, equivocal on clinical grounds alone, were first detected by a low value in screening tests for serum thyroxine levels and subsequently confirmed by a high serum TSH level. Low serum triiodiothyronine level is frequently found in apparently euthyroid patients with tetraplegia and is necessarily not an indicator of clinical hypothyroidism in these patients.

Adolescent↗