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Biomedical subjects

L Tan

Publications and source records attributed to L Tan.

At least 199 records · Page 11Linked to original sources
PubMed1985

Purification of oestrogen synthetase by high-performance liquid chromatography. Two membrane-bound enzymes from the human placenta.

Human placental NADPH-cytochrome P-450 reductase, obtained by 2',5'-ADP-Sepharose affinity chromatography, was separated into two reductase-active peaks on a Pharmacia Mono-Q column. By this short, two-step chromatographic procedure, the two reductases were obtained in a homogeneous state with high retention of activity and in over 900-fold purification. Aromatase-reconstituting activity was present only in the higher-molecular-weight reductase (79 000 D), not in the smaller, 70 000 D reductase, which turned out to be a proteolysis product of the former. Both proteins were eluted as a single peak in reversed-phase high-performance liquid chromatography on a Protesil-diphenyl column. Similar results were obtained with bovine hepatic NADPH-cytochrome P-450 reductases. On the other hand, starting from a reductase-free preparation, we have obtained by high-performance ion-exchange chromatography and high-performance size-exclusion chromatography, only partial purification of the aromatase cytochrome P-450, which showed the following values: aromatase activity, 3.995 nmol/min/mg protein (60-fold purification); cytochrome P-450 content, 1.376 nmol/mg protein (23-fold purification); molecular weight, 165 000 D (estimated as an aggregate by size-exclusion chromatography). Although complete purification of the aromatase component has yet to be accomplished, our results suggest that high-performance ion-exchange chromatography on a Mono-Q column is very useful for the purification of acidic, membrane-bound enzymes with good retention of activity.

Ammonium Sulfate↗
PubMed1985

Inactivation of human placental aromatase by 6 alpha- and 6 beta-hydroperoxyandrostenedione.

The epimeric 6 alpha- and 6 beta-hydroperoxy derivatives of androstendione caused irreversible inactivation of human placental aromatase. Microsomes from term-placentae were first preincubated in the presence of increasing concentrations of the hydroperoxides. The microsomes were then washed free of steroids and its residual aromatase activity was assayed by the tritium-exchange method to [3H]water. Aromatase activity decreased in a time-, and concentration-dependent manner; the axial, beta-hydroperoxy epimer was the slightly stronger inactivator. Less inactivation occurred when during the preincubation stage the natural aromatase substrate, androstenedione, or the anti-oxidant, dithiothreitol, was added. The sulfhydryl reagent, p-hydroxy-mercuribenzoate, decreased this protective effect. The inactivation is not dependent on the presence of NADPH. Both steroids induced a Type I difference spectrum with a Ks of 0.167 microM and 0.163 microM for the 6 alpha-, and the 6 beta-hydroperoxyandrostenedione, respectively. We suggest that these 6-hydroperoxyandrogens may function as active-site directed inhibitors and inactivators of estrogen synthetase through oxidation of cysteine residues.

Androstenedione↗
PubMed1985

Quantification of mitral valvular incompetence.

The hemodynamic and angiographic data of 147 individuals were analyzed in an attempt to assess the value of three techniques used in the diagnosis of mitral incompetence. One hundred patients had clinical evidence of mitral incompetence (group A) and 47 had normal hemodynamics (group B). The degree of mitral incompetence was assessed in all 147 individuals by two methods: determination of a regurgitant index (RI) using indicator dilution curves and determination of a regurgitant fraction (RF) using left ventricular volumes. In 26 patients of group A and 26 individuals in group B mitral incompetence was also assessed by cineangiocardiography. Each of these methods was compared with the clinical and hemodynamic evidence of mitral valvular incompetence. Both the determination of RI by dye dilution curves and RF by angiocardiography were found to be useful in separating normal individuals from patients with mitral valvular incompetence. Severe mitral incompetence is associated with an RI greater than 35% and with an RF greater than 55%. The degree of incompetence by either method was not well correlated with any independent hemodynamic variable. The use of cine angiocardiography to quantify the degree of mitral incompetence was found to be too subjective, depending on the observer, and thus less useful.

Adult↗
PubMed1985

CSF shunt complications: an analysis of contributory factors.

The complications arising from 195 shunting procedures are described and correlated with patient and operative variables. Neither the patient's age, sex, type of hydrocephalus, length of surgery, nor the use of prophylactic antibiotics correlated significantly with subsequent shunt complications. However, the surgeon performing the procedure and the type of shunt used were highly significant correlates.

Adolescent↗
PubMed1984

De novo biosynthesis of 6 beta-hydroperoxyandrostenedione in human placental microsomes.

Fresh human placental microsomes were incubated at 37 degrees C with a homogeneous mixture of tritium labeled 4-androstene-3,17-dione and unlabeled 6 beta-hydroperoxy-androstenedione in the presence, or absence, of various inhibitors. In all cases, radioactive 6 beta-hydroperoxyandrostenedione could be trapped in amounts significantly different from carefully conducted controls. The radioactive purity of the hydroperoxide formed was established by repetitive HPLC purifications whereby a constant ratio of radioactive counts versus peak area was obtained. The amount of tritiated 6-bèta-hydroperoxyandrostenedione produced was dependent both on the incubation time and on the microsomal protein concentration used. It was also found that in the complete absence of air, the unlabeled hydroperoxide could act as oxygen donor, supporting the formation of radioactive, 6-oxygenated metabolites. These findings are fully consistent with the concept that 6-bèta-hydroperoxyandrostenedione acts as an endogenous precursor in the formation of the corresponding 6 beta -hydroxy and 6-oxo androstene metabolites in the human placenta; a fact not previously recognized.

Androstenedione↗
PubMed1984

Serum levels of C-reactive protein in neonatal respiratory distress syndrome.

Serum levels of C-reactive protein (CRP) were measured within 96 hours of birth in 55 neonates with respiratory distress syndrome (RDS), 19 neonates with no significant medical illness other than an unstable cardiovascular state, and 13 neonates with a variety of pulmonary and extra-pulmonary problems either alone or in combination with RDS. The median serum CRP level in patients with RDS (2 micrograms/ml) was neither elevated nor different from CRP levels in infants with unstable cardiovascular systems (median CRP level, 2 micrograms/ml); however, neonates with other problems including pneumonia, aspiration, and extrapulmonary sepsis had significantly elevated serum CRP values (median 24 micrograms/ml). CRP levels are not elevated in neonatal RDS. Measurement of this acute phase reactant provides a rapid and reliable means of helping to distinguish infants with uncomplicated RDS from those with other serious pulmonary and extrapulmonary disease.

C-Reactive Protein↗
PubMed1984

Two-dimensional and pulsed Doppler echocardiographic abnormalities in coronary artery-pulmonary artery fistula.

We describe two patients who presented with precordial continuous murmurs which were diagnosed clinically as due to patent ductus arteriosus; however, two-dimensional echocardiographic and pulsed Doppler echocardiographic studies showed dilatation of the left main coronary artery with turbulent flow during systole in the lumen in both patients. Subsequent selective coronary angiographic studies showed bilateral coronary artery-pulmonary artery fistula in one patient and left coronary artery-pulmonary artery fistula in the other. This study illustrates that in a patient presenting with a continuous murmur which is suggestive of patent ductus arteriosus, such two-dimensional and pulsed Doppler echocardiographic findings as were seen in our patients should immediately alert the physician that he may be dealing with a case of coronary arterial fistula.

Coronary Vessels↗
PubMed1983

Synthesis and properties of the epimeric 6-hydroperoxyandrostenediones, new substrates/inhibitors of human placental aromatase.

We have recently reported the formation in bovine adrenals and in rat liver of 6 beta-hydroxy-, and 6-oxoprogesterone via the 6 beta-hydroperoxy intermediate. The presence of steroid hydroperoxides in animal tissues, however transient it may be, is not devoid of physiologic significance in view of their characteristic property as potential radical initiators. Since 6-hydroperoxides of androgens have not previously been described, we have synthesized the 2 epimeric 6 alpha-, and 6 beta-hydroperoxy-4-androstene-3,17-diones by oxygenation of 5-androstene-3,17-dione in an aprotic solvent system in the presence of dibenzoyl-peroxide. Their chemical identity and chirality were established by IR, NMR, GC-MS, and by reduction to the known 6 alpha and 6 beta-alcohols. These hydroperoxide stereoisomers could only be separated without decomposition by HPLC using a non-aqueous mobile phase. In our search for a natural, non-estrogenic inhibitor of human placental aromatase, we have studied the effect on this enzyme complex of 6 alpha- and 6 beta-OOH-androstenedione, as well as of their corresponding 6-hydroxy and 6-oxo metabolites. Aromatase activity was measured by a slightly modified version of Thompson and Siiteri's original assay based on 1 beta,2 beta-tritium exchange to 3H water. The C-6 oxygenated androgens were found to competitively inhibit the aromatase reaction in the following descending order: 6-oxo greater than 6 beta-OH greater than 6 alpha-OOH greater than 6 beta-OOH showing Ki values of resp. 2.5, 5.0, 6.5 and 7.5 microM, suggesting that they are interacting with the same active site. Moreover, both 6 alpha- and 6 beta-hydroperoxyandrostenedione are active substrates for the aromatase, giving KM values of 2.8 and 2.5 microM respectively.

Androstenedione↗
PubMed1983

Cranial volume and occipito-frontal circumference in neonates.

Occipitofrontal head circumference (OFC), using tape, and calibrated scale and cranial volumes, using styrofoam plastic cast, were measured in nine preterm and 13 term infants. Term infants had a mean +/- S.E. gestation of 40 +/- 0.2 wk and a mean +/- S.E. birth weight of 3461 +/- 108 g. Preterm infants had a mean +/- S.E. gestation of 30.5 +/- 1.4 wk and a mean +/- S.E. birth weight of 1596 +/- 211 g. Five sequential measurements were made on term infants and nine such measurements were done on preterm infants at specified time intervals. The values of cranial volume were compared with previously published results in term infants. Brain weight and cranial volumes were also compared in 10 preterm infants and seven term infants who died of non-intracranial pathology. To determine if this method is reproducible, it was tested using 50 paired measurements and was found to be within 3%. There was a significant decrease in cranial volume in term and preterm infants with time. Term infants reached the control value at 64 h of age and preterm infants reached the control value at 160 h of age. Preterm infants showed a significant decrease in OFC but term infants did not. The rate of change was not significantly different in either group.(ABSTRACT TRUNCATED AT 250 WORDS)

Brain↗
PubMed1982

Chronic lymphocytic leukemia. A review of 745 cases and assessment of clinical staging.

Review of 745 cases of chronic lymphocytic leukemia show that clinical staging by either the Rai or Binet method is very valuable in assessment of patients at the time of diagnosis. There is a marked decrease in survival with advancing stage (19.9 years median survival for Rai Stage 0, and 2.5 years and 2.7 years for Rai Stages 3 and 4, respectively). The definition of anemia as Hb less than 11 g/dl as in the Rai staging method appears to give slightly better discrimination among the stages than the Binet staging procedure. Patients with splenomegaly alone (Binet stage 2), however, form a small but distinct group that should be recognized. These is little to be gained by subdividing further according to size of the lymph nodes.

Adult↗