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Biomedical subjects

M S Lin

Publications and source records attributed to M S Lin.

177 records · Page 10Linked to original sources

Kinetics of amino acid transport across bone marrow cell membranes.

Dog bone marrow nucleated cells were incubated in media containing labeled L-amino acids, and the cellular accumulation of radioactivity as a function of time was measured and analyzed according to a three-compartment model.(a) The turnover half-time of intracellular histidine arising from extracellular sources was 6.0 +/-0.7 (SEM) min. Similar turnover half-time for serine was 10 +/-2 (SEM) min; for tryptophan, 6.5 +/-1.2 (SEM) min; and for methionine, 4.4 +/-0.6 (SEM) min. Loss of the intracellular amino acids to the extracellular space accounted for the major portion of their turnover.(b) Each of the four amino acids noted above appeared to be actively transported into the cell.(c) At physiologic extracellular histidine concentrations, histidine entered the cell predominantly by a facilitated process with an apparent Michaelis constant of 0.28 mmole/liter and a limiting flux of 14 x 10(-8) mmumole/min per cell. Loss of histidine from the cell appeared to be substantially facilitated with an apparent Michaelis constant greater than that for histidine entry.(d) Insulin and glucagon had no measurable effect on histidine transport across the bone marrow cell membrane.(e) Methionine depressed the influx and the fractional turnover rate of the intracellular pool of both histidine and serine.(f) The extent of cellular accumulation of alpha-N-formiminoglutamate and alpha-N-formylglutamate was about 1/100 that of histidine. alpha-N-formiminoglutamate added to the culture was about (1/4) as effective as histidine in providing monocarbon fragments for DNA thymine synthesis.

Amino Acids↗

The prenatal detection of the fragile X chromosome: review of recent experience.

The fragile X chromosome has been identified in specimens from 17 male and 10 female fetuses in 11 laboratories throughout the world, obtained from at least 79 fetuses at increased risk for the fra(X) syndrome. Of these, 19 were confirmed, 6 were pending, 1 was negative and 1 could not be confirmed. Twenty-five of the 79 cases were studied in our laboratory (Institute for Basic Research [IBR]) and resulted in fra(X) demonstration in specimens from 3 male and 5 female fetuses. All 3 males and 2 of the 5 females have been confirmed. When amniocytes from the two confirmed female fetuses were exposed to FUdR after culturing in Chang medium, fra(X) frequencies were virtually negative indicating that Chang medium should not be used in fragile X studies at least when FUdR is used to induce fragility. Finally, amniocytes from a fra(X) male fetus studied in 3 different laboratories exhibited strikingly different frequencies. To date, we have experienced no false-positives or negatives, but the latter case was controversial. It is recommended that laboratories undertaking fra(X) prenatal detection use a combination of at least two different proven induction systems as well as complementary DNA marker studies to prevent false negative diagnosis.

Amniocentesis↗

Herpes gestationis.

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Female↗

A study of o-cresolphthalexon and its analogs as cholescintigraphic 111In carriers.

111In has been complexed to a series of metal-complexing phthaleins and sulfonphthaleins, and the hepatobiliary excretion of the compounds were compared in rats. The highest biliary excretion was obtained with 111In-o-cresolphthalexon. In a normal human subject, sequential imaging with 111In-o-cresolphthalexon visualized his gallbladder, common bile duct, and the bowel from jejunum to rectum. The potential utility and limitation of this biliary scanning agent is discussed.

Adult↗

A rare 6q11+ heteromorphism: cytogenetic analysis and in situ hybridization.

A rare variant of 6q11+ heteromorphism was found in a fetus and the mother during amniocentesis. The G- and Q-banding and DA/DAPI stain were negative. The C-banding was positive and the C-banded segment was 3-fold longer in the variant than in its homologue. Neither of the C-banded regions of chromosomes 6 decondensed when exposed to distamycin A or 5-azacytidine. A DNA replication study indicated that the C-banded variant was late replicating. The lateral asymmetry observed in the 6q11 variant after one replication cycle in 5-bromodeoxyuridine may result from an unequal interstrand distribution of thymidine in the repetitive DNA. Fluorescent in situ hybridization using a chromosome-6-specific alpha-satellite probe (D6Z1) demonstrated hybridization signals on the centromere of chromosome 6. The 6q11 variant showed a signal which was 3-fold larger than its homologue. These results indicate that the 6q11 variant is an amplification of a chromosome-6-specific alpha repeat, and the size of the hybridization signal correlates with the size of the laterally asymmetric and C-banded region.

Amniocentesis↗

Plasma concentration and acetylator phenotype determine response to oral hydralazine.

The vasodepressor response to single and multiple oral doses of hydralazine, 1 mg/kg, was studied in hypertensive patients. The concentration of hydralazine in plasma was measured both by a newly developed specific and a nonspecific assay similar to those used in previous studies. Acetylator phenotype was determined following oral sulfamethazine. Plasma hydralazine concentration peaked at 1 hour after administration and was undetectable 2 hours later. Apparent hydralazine was present in plasma in higher concentration and for a longer duration than hydralazine. The peak decreases in blood pressure (BP) were proportional to plasma hydralazine concentration following administration of both single and multiple doses and were substantially maintained for 8 hours. In contrast there was no significant correlation between decreases in BP and apparent hydralazine concentrations. The plasma concentration of hydralazine after a standard oral dose varied by as much as 15-fold among individuals and was lower in rapid than slow acetylator phenotype patients. The BP responses were positively correlated with plasma hydralazine concentrations and inversely correlated with acetylator indices. Low plasma concentrations may account for poor responses of some patients to conventional oral doses of hydralazine. The applicability of acetylator phenotyping for individualization of hydralazine dosage regimens merits further evaluation.

Acetylation↗

Baroreflex sensitivity modulates vasodepressor response to nitroprusside.

Baroreflex activity is a determinant of the homeostatic response to alteration in blood pressure. We examined the factors that determine the magnitude of the vasodepressor response to sequential incremental intravenous infusions of sodium nitroprusside (NP), 0.05 to 6.4 micrograms/kg/min, in eight male patients with essential hypertension. Each infusion level was of 10 minutes' duration. Change from control values of mean arterial pressure (delta MAP), heart rate (delta HR) and plasma norepinephrine (delta NE) were obtained at the end of each infusion level. Significant correlations were found between delta MAP vs log dose NP, delta HR vs delta MAP and delta NE vs delta MAP for each patient (p less than 0.05). However, the slopes of these relationships varied widely between subjects and were significantly correlated with the control blood pressure of each patient. In addition, the sympathetic responsiveness, as measured by delta NE vs delta MAP, was inversely correlated with the degree of vasodepressor response seen. Thus, the magnitude of the vasodepressor response was determined by two major factors: 1) the predrug blood pressure, possibly reflecting altered vascular geometry with hypertension; 2) the degree of sympathetic response, which probably acts by mediating the degree of reflex alpha-adrenergic-mediated arteriolar vasoconstriction.

Blood Pressure↗

Increased plasma norepinephrine accompanies persistent tachycardia after hydralazine.

To determine the role of the peripheral sympathetic nervous system in the persistent tachycardia caused by the antihypertensive drug hydralazine, we examined the temporal relationships between the changes in heart rate and plasma norepinephrine concentration and the reduction in blood pressure produced by a range of doses of hydralazine administered intravenously to five hypertensive patients. Significant linear correlations were found between the increases in heart rate and plasma norepinephrine concentration and the reduction in blood pressure at 15 and 30 minutes after injection. However, at 240 minutes after injection, changes in heart rate and plasma norepinephrine were not correlated with changes in blood pressure and were disproportionately elevated relative to the reduction in blood pressure. A significant linear correlation between changes in heart rate and plasma norepinephrine concentration was noted at 15, 30, and 240 minutes after injection. The temporal discordance of the changes of both heart rate and plasma norepinephrine relative to the reduction in blood pressure and the significant linear correlation between the increases in heart rate and plasma norepinephrine concentration suggest that continued activation of the peripheral sympathetic nervous system contributes to the persistent tachycardia seen after the administration of hydralazine.

Blood Pressure↗

Effect of anti-hypertensive drug dose frequency on the clinic-home blood pressure difference in patients with stage 1 treated hypertension.

Clinic blood pressure (CBP) is generally used for diagnosis and treatment monitoring in hypertension, but target organ damage correlates more closely with home blood pressure (HBP). Eliminating the clinic-home blood pressure difference (CHBPD) would make conventional CBP a more accurate alternative to HBP. This prospective, randomized, open trial compared the effect of a once-daily versus a twice-daily regimen of anti-hypertensive therapy on CHBPD. After a 2-week wash-out period, 85 confirmed stage 1 hypertensive patients were randomized to receive 2 mg trichlormethiazide daily in one (40 subjects) or two (45 subjects) daily doses for 3 weeks. CBP and HBP measurements were taken during the third week of treatment and the CHBPD calculated. After treatment, the systolic and diastolic CHBPD values were significantly greater in the once-daily regimen than in the twice-daily regimen. Conventional CBP should not be used as an alternative to HBP for evaluating prognosis and monitoring anti-hypertensive therapy when using a once-daily regimen.

Adult↗

Activation of the renin-angiotensin system by sodium nitroprusside in essential hypertension.

We previously have demonstrated that the sympathetic nervous system is activated proportionately to the degree of vasodepression induced in hypertensive patients. In the present study, the role of the renin-angiotensin system in modulating the vasodepressor response to sodium nitroprusside was examined. Nine hospitalized hypertensive patients receiving a diuretic were given serially incremental doses of sodium nitroprusside over a dose range of 0.05-4.8 micrograms/kg/min with each dose being infused for 10 min. Mean arterial pressure (MAP), heart rate (HR), plasma renin activity (PRA), and plasma norepinephrine (NE) concentration were measured prior to and during each dose level of sodium nitroprusside. Stepwise increments in PRA were seen in each patient as the dose of sodium nitroprusside was increased. The increase in PRA was proportional to the increase in plasma NE concentration and to the decrease in MAP in each patient. However, considerable intersubject variation was seen in these relationships. When examined by multiple linear stepwise regression analysis, the degree of vasodepression was found to be dependent on the baseline blood pressure and baroreflex sensitivity (r = 0.97). However, increment in PRA was not an independent determinant of the vasodepressor response. Thus, the renin angiotensin system may not be a significant component of the acute homeostatic response to vasodepression in these patients.

Blood Pressure↗