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Biomedical subjects

L Nguyen

Publications and source records attributed to L Nguyen.

At least 145 records · Page 8Linked to original sources

Feedback regulation of bile-acid synthesis in the rat. Differing effects of taurocholate and tauroursocholate.

We studied the effect of the orientation of the 7-hydroxyl group in taurocholate (7 alpha) and tauroursocholate (7 beta) on the feedback regulation of bile-acid synthesis and its rate-controlling enzyme, cholesterol 7 alpha-hydroxylase, in bile-fistula rats. To ensure a constant supply of cholesterol and to label newly synthesized bile acids, RS[2-14C]mevalonolactone was infused intraduodenally at 154 mumol/h before and during bile-acid infusion. Mevalonolactone inhibited hydroxymethyl-glutaryl CoA reductase activity 90% but did not increase bile-acid synthesis and cholesterol 7 alpha-hydroxylase activity. When sodium taurocholate was infused at the rate of 27 mumol/100 g rat per h (equivalent to the hourly hepatic bile-acid flux), bile-acid synthesis decreased 82% and cholesterol 7 alpha-hydroxylase activity declined 78%. This inhibitory effect was observed in the absence of hepatic damage. In contrast, sodium tauroursocholate infused at the same rate did not decrease bile-acid synthesis nor cholesterol 7 alpha-hydroxylase activity. Hepatic cholesterol content rose 36% with sodium taurocholate but did not change during sodium tauroursocholate administration. These results demonstrate that the feedback inhibition of bile-acid synthesis is mediated through the regulation of cholesterol 7 alpha-hydroxylase. In these experiments, taurocholate was a far more potent inhibitor than its 7 beta-hydroxy epimer, tauroursocholate.

Animals↗

Prostatic acid phosphatase in serum of patients with prostatic cancer is a specific phosphotyrosine acid phosphatase.

We developed an assay to measure at acid pH the phosphotyrosine phosphatase activity in sera from patients with prostatic cancer. The method used quantifies the inorganic phosphate liberated from phosphotyrosine after incubation with serum, followed by the deproteinization of the reaction mixture. A high acid phosphatase (EC 3.1.3.2) activity towards phosphotyrosine was observed in all sera from patients with increased activity of prostatic acid phosphatase. This activity represented 96% of prostatic acid phosphatase and 77% of total acid phosphatase activities. Moreover, it was correlated (r = 0.91) with the amount of serum prostatic acid phosphatase determined by radioimmunoassay. When serum acid phosphatase activity was measured on several phosphorylated substrates, preferential hydrolysis was demonstrated for those in which the phosphate group was esterified on an aromatic ring rather than those presenting an aliphatic chain. Among phosphoamino acids, only phosphotyrosine was a good substrate, with little or no activity observed with phosphoserine and phosphothreonine. Human seminal plasma and partially purified prostatic acid phosphatase, tested for their activity on some of these substrates, gave similar results. On the other hand, sera from patients with above-normal alkaline phosphatase activity and no prostatic disease showed little or no activity on phosphotyrosine at both acid and alkaline pH values. Evidence is presented that the prostatic acid phosphatase in serum is a specific phosphotyrosine acid phosphatase.

Acid Phosphatase↗

Practice patterns, attitudes and activities of Caucasian vs. Asian University of California-San Francisco PharmD graduates.

The results of a 1982 survey of graduates of the University of California at San Francisco (UCSF) doctor of pharmacy degree program were re-analyzed to explore whether cultural differences between Asian and Caucasian PharmD graduates affected professional practice patterns, attitudes and activities. Of the 732 respondents, 408 (56 percent) were Caucasians and 262 (36 percent) were Asians. Asian females had significantly fewer years of college education before entering pharmacy school and spend significantly fewer hours in the practice of pharmacy or related activities. Caucasians had a slightly higher grade point average than Asians. The mean score on the California State Board of Pharmacy Licensure Examination did not differ between the groups. For their first position following graduation, Asians predominated in operational positions, while Caucasians held clinical positions more frequently. Thirty-eight percent of Caucasians vs. 18 percent of Asians were taking or had completed postgraduate residency or fellowship training. An analysis of current jobs revealed that Asian males had the greatest increase in clinical positions when compared to the first position. Males of both ethnicities made the greatest gains in annual salary and in management positions compared to females.

Asian↗

Increased sitosterol absorption, decreased removal, and expanded body pools compensate for reduced cholesterol synthesis in sitosterolemia with xanthomatosis.

We measured the turnover and absorption of sitosterol and cholesterol, along with plasma sterol and lipoprotein concentrations, in one control and two subjects with sitosterolemia with xanthomatosis. All individuals consumed the same diet which contained approximately 500 mg/day of cholesterol and 250 mg/day of sitosterol. Sterol absorption was measured by the plasma dual-isotope ratio method and turnover by plasma isotope-kinetic analysis. In two sitosterolemic subjects, 28% and 63% of the sitosterol and 69% and 49% of the cholesterol were absorbed, respectively, compared to 4% of the sitosterol and 44% of the cholesterol in the control. As expected, plasma sitosterol specific activities decayed much more rapidly than cholesterol in the control subject. In contrast, plasma sitosterol and cholesterol specific activity-time curves were similar and decayed more slowly in the sitosterolemic subjects. In the control subject, the total sitotterol pool was 290 mg and was linearly related to low absorption (18 mg/day); whereas the total sitosterol pool was 17 times (4800 mg) and 13 times (3500 mg) larger, respectively, in the sitosterolemic subjects and was expanded out of proportion to increased absorption because of decreased removal. Daily cholesterol turnover and synthesis were markedly reduced in the sitosterolemic subjects. In four sitosterolemic subjects, plasma concentrations of total sterols, low density lipoproteins, and apolipoprotein B were increased, while those of high density lipoproteins and apolipoprotein A-I were low to normal. The low density lipoproteins were very similar to those of normal control subjects in density distribution, peak flotation rate, sterol-to-protein (apolipoprotein B) ratio, particle size, and morphology. These results demonstrate in patients with sitosterolemia with xanthomatosis that: 1) the absorption of sitosterol and cholesterol is enhanced; 2) tissue recognition between cholesterol and sitosterol is lost; 3) total exchangeable sitosterol pools are expanded out of proportion to absorption because of decreased excretion; 4) plasma sterol and lipoprotein concentrations favor tissue deposition; and 5) cholesterol synthesis is diminished. We postulate that the changes in sitosterol metabolism (increased absorption, loss of tissue sterol structural recognition, expanded pools, and hepatic retention) are a response to reduced cholesterol synthesis in these subject.

Absorption↗

Two classes of N-methyl-D-aspartate recognition sites: differential distribution and differential regulation by glycine.

The N-methyl-D-aspartate (NMDA) receptor, a subtype of excitatory amino acid receptor, mediates synaptic responses in many regions of the central nervous system. This receptor plays a critical role in the mechanisms of both synaptic plasticity and excitotoxicity. Although these receptors were generally thought to be a single homogeneous receptor population, we report observations indicating that two anatomically distinct forms of the NMDA-receptor complex exist. (i) The distribution of NMDA receptors, as labeled by the NMDA agonist L-[3H]glutamate, differs from that obtained with the radiolabeled antagonist 3H-labeled 3-[(+/-)2-carboxypiperazine-4-yl]propyl-1-phosphonic acid [( 3H]CPP). Relative to L-[3H]glutamate, [3H]CPP binding is low in the striatum and septum and high in the thalamus and inner cerebral cortex. (ii) NMDA antagonists are relatively more potent than agonists at displacing L-[3H]glutamate binding in the thalamus and cerebral cortex; agonists are relatively more potent in the striatum and cerebellum. (iii) Glycine, which potentiates NMDA-receptor responses to glutamate, causes a greater percentage increase in L-[3H]glutamate binding to NMDA receptors in the thalamus and cerebral cortex than in the striatum, septum, and cerebellum. Radiolabeled NMDA-antagonist binding, in contrast, is inhibited by glycine. Thus, as observed for gamma-aminobutyric acid type A receptors, NMDA receptors have an agonist-preferring binding-site population and an antagonist-preferring binding site population. These may represent two distinct receptors and/or two interconverting forms. It could be of significant clinical importance if these two sites differ in their response to NMDA.

Animals↗

Competitive inhibition of bile acid synthesis by endogenous cholestanol and sitosterol in sitosterolemia with xanthomatosis. Effect on cholesterol 7 alpha-hydroxylase.

The 7 alpha-hydroxylation of two cholesterol analogues, sitosterol and cholestanol, and their effect on the 7 alpha-hydroxylation of cholesterol were measured in rat and human hepatic microsomes. In untreated rat liver microsomes, the 7 alpha-hydroxylation of cholesterol was higher than that of cholestanol (1.4-fold) and sitosterol (30-fold). After removal of endogenous sterols from the microsomes by acetone treatment, the 7 alpha-hydroxylation of cholesterol was similar to that of cholestanol and only fourfold higher than that of sitosterol. Cholestanol and sitosterol competitively inhibited cholesterol 7 alpha-hydroxylase in both rat and human liver microsomes, with cholestanol the more potent inhibitor. Patients with sitosterolemia with xanthomatosis, who have elevated microsomal cholestanol and sitosterol, showed reduced cholesterol 7 alpha-hydroxylase activity relative to the activity in control subjects (13.9 and 14.7 vs. 20.3 +/- 0.9 pmol/nmol P-450 per min, P less than 0.01). Enzyme activity in these patients was 40% higher when measured in microsomes from which competing sterols had been removed. Ileal bypass surgery in one sitosterolemic patient decreased plasma cholestanol and sitosterol concentrations and resulted in a 30% increase in hepatic microsomal cholesterol 7 alpha-hydroxylase activity. Cholesterol 7 alpha-hydroxylase appears to have a specific apolar binding site for the side chain of cholesterol and is affected by the presence of cholestanol and sitosterol in the microsomal substrate pool. Reduced bile acid synthesis in sitosterolemia with xanthomatosis may be related to the inhibition of cholesterol 7 alpha-hydroxylase activity by endogenous cholesterol analogues.

Adolescent↗

An Intelligent Display System for psychiatric education in primary care.

We have shown how new concepts for displaying knowledge and data may overcome some of the limitations of existing decisionmaking and educational aids and how they may improve psychiatric diagnosis and education. Elsewhere, we illustrated how these concepts can also be applied in redesigning ordinary textbooks in many other areas of medicine. Using such ideas to simplify decisionmaking without oversimplifying and without reducing physician participation may help us to cope with the enormous growth of information and knowledge. This is a problem common to many areas of medicine, one that demands new ways of thinking about how to simplify educational methods.

Computer-Assisted Instruction↗

The distribution of [3H]kainate binding sites in primate hippocampus is similar to the distribution of both Ca2+-sensitive and Ca2+-insensitive [3H]kainate binding sites in rat hippocampus.

The distribution of [3H]kainate binding sites was determined by quantitative autoradiography in three vertebrate species: rat, monkey, and human. These animals displayed a similar pattern of binding site density in the hippocampus. Highest levels were found within the stratum lucidum and moderate levels in the inner portion of the dentate gyrus molecular layer. Although the distribution is similar, there is a lower density of binding sites in the stratum lucidum of primates than in rodents. Experiments using rat brain synaptic plasma membrane fractions indicated that inclusion of Ca2+ ions results in a selective reduction in binding at the high affinity sites. The Ca2+-inhibited and Ca2+-inhibited binding sites in the high affinity sites. The Ca2+ -inhibited and Ca2+ -insensitive binding sites in the rat hippocampus exhibited a similar distribution. Together, these results suggest that in a variety of mammalian species kainate receptors exhibit similar regional distributions, and that the high and low affinity kainate binding sites also exhibit similar regional distributions.

Autoradiography↗

[Treatment of epitheliomas of the parotid. Apropos of 93 cases treated at the Curie Institute].

From 1955 through 1982, a series of 93 cases of parotid gland carcinoma were treated at the Institut Curie: 55 primarily and 28 for recurrent tumors. Treatment modalities included surgery alone (n : 14), surgery followed by radiotherapy (n : 43), and radiotherapy alone (n : 36). The most advanced cases were mostly in the latter group. With a mean follow-up of 13 years, the actuarial loco-regional control is 67% (62/93) and the median survival 10 years. Ultimate loco-regional control was achieved in 86% of cases managed by surgery alone, 88% of cases managed by surgery and radiotherapy and 33% of cases managed by radiotherapy. In the latter group, control rate was 42% (8/19) in those primarily treated by radiotherapy. Prognosis was related to histology. Twenty patients (22%) presented distant metastasis. The potential advantages of neutron irradiation for parotid neoplasms is discussed.

Adolescent↗

[Can the quality and duration of life be integrated? Proposal for a new criterion for decision].

Survival is an objective criteria, reliable, easy to measure and easy to analyse. But this criteria, the most important in almost all therapeutic trials, is a very rough one and not all fitted to many questions raised in cancer treatment decision making. We suggest a new criteria, combining quality and quantity of survival, which is equivalent in years of survival at a maximal quality level to the time of survival at a varying level of a cancer patient. This criteria could be usefull in the majority of "palliative" clinical trials (advanced cancers, recurrences, metastatic evolution...).

Antineoplastic Combined Chemotherapy Protocols↗

Laryngotracheoesophageal cleft. An easily missed malformation.

Laryngotracheoesophageal cleft is a rare congenital anomaly characterized by a midline defect of variable length between the posterior larynx and trachea and the anterior wall of the esophagus. This report concerns the clinical course and follow-up of three patients with this anomaly and a review of the literature. Only one of these patients had a successful repair on the first attempt. The difficulty in making the diagnosis is stressed. This anomaly is associated with a high morbidity and mortality.

Diagnostic Errors↗

Hydrometrocolpos in neonate due to distal vaginal atresia.

Hydrocolpos is the result of vaginal obstruction and can become an emergency in the newborn period. The treatment of imperforate hymen is well defined, but the treatment of vaginal atresia is more complex. We encountered two cases of hydrocolpos secondary to distal vaginal atresia, that were operated on in the first days of life. One baby had distal atresia without persistance of urogenital sinus. Surgery combining abdominal perineal approaches and a posterior vaginoplasty was carried out. The second baby had hydrocolpos with persistance of urogenital sinus. Drainage through the sinus was unsuccessful because the baby developed sepsis by trapping urine in the uterus. Finally an abdominoperineal vaginal pull-through was successfully done. The embryology and literature are reviewed. The classification, indications and surgical technique are discussed.

Female↗

Segmental dilation of the colon: a rare cause of chronic constipation.

Segmental dilation of the colon is a rare entity. It should be considered in any young patient with chronic constipation. The clinical picture and radiographic examination are indistinguishable from Hirschsprung's disease and the rectal biopsy is of paramount importance. This disease can be cured by resection of the dilated segment.

Child↗

Head and neck manifestations of the chronic graft vs. host disease.

Bone marrow transplantations are being used with increasing frequency in the treatment of patients with leukemia and aplastic anemia. The graft-vs.-host disease (GVHD) is a serious complication that affects long-term survivors following bone marrow transplantation. It is the result of an immunologic reaction mounted by the grafted reticuloendothelial cells against the tissues of the recipient, and it affects multiple organ systems. Involvement of the skin and mucosal surfaces of the head and neck region, in particular the oral cavity, occurs in a large number of patients with GVHD. In this report we present four patients with GVHD in whom mucosal lesions and infections of the head and neck region were prominent features. Our observations indicate that the clinical and histological characteristics of these lesions vary according to the time elapsed from the onset of the disease. Therefore, clinical examination of the head and neck region and biopsy of the oral mucosa are important not only in the diagnosis of the GVHD, but also in the evaluation of its progress and response to treatment.

Adult↗

The mortality of congenital diaphragmatic hernia. Is total pulmonary mass inadequate, no matter what?

Much progress has been made over the past 20 years in neonatal surgery, but the mortality rate in cases of congenital diaphragmatic hernia (CDH) for babies presenting in the early hours of life has remained high. We have reviewed our experience with special reference to 40 autopsied patients. Hypoplastic lungs were seen in all patients. When the ratio of observed combined lung weight to the expected combined lung weight is calculated, the result is 0.33 +/- 0.17 when the expected lung weights are calculated from the babies' birth weight; and 0.36 +/- 0.17 when the expected lung weights are calculated from the gestational age. In all patients with high ratios, extensive pneumonia was confirmed. Those patients with pneumonia were eliminated from the calculations. We cannot state unequivocably that hypoplasia of both lungs is the cause of death in all patients with CDH. We can affirm that, in our experience, hypoplasia is present and is probably a major factor in the high mortality rate.

Hernia, Diaphragmatic↗