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Biomedical subjects

T H Tran

Publications and source records attributed to T H Tran.

At least 37 records · Page 2Linked to original sources

Blackwater fever in southern Vietnam: a prospective descriptive study of 50 cases.

We prospectively studied 50 Vietnamese patients with blackwater fever (BWF). All patients had fever and hemoglobinuria, 40 (80%) were jaundiced, 25 (50%) had hepatomegaly, 15 (34%) had splenomegaly, and 9 (18%) had hepatosplenomegaly. Twenty-one patients (42%) had impaired renal function, with creatinine clearances of < 50 mL/min/m2; however, only four (8%) developed oliguric renal failure, three (6%) of whom required dialysis. Forty-four patients (88%) developed anemia, which was severe (hematocrit, < 20% in 32 (64%). One patient died, representing a death rate for this once-feared disease that is considerably lower than that reported by earlier investigators. BWF was associated with quinine ingestion in 28 patients (56%), glucose-6-phosphate dehydrogenase (G6PD) deficiency in 27 (54%), and concurrent malaria infection in 16 (32%). There was no statistically significant difference in the severity of BWF associated with each of these three factors, as assessed by creatinine clearance and the hematocrit value on admission and by the number of units of blood transfused. There was considerable overlap in the occurrence of G6PD deficiency, quinine ingestion, and malaria, suggesting that these factors may interact and that it may not be justifiable to regard hemoglobinuria caused by G6PD deficiency as a separate syndrome.

Blackwater Fever↗

Characterization of the murine mu opioid receptor gene.

The analgesic and addictive properties of morphine and other opioid drugs are thought to result from their interaction with mu opioid receptors. Using a delta opioid receptor cDNA as a probe, we have isolated a murine mu opioid receptor cDNA clone (mMOR). Stable expression of mMOR in Chinese hamster ovary cells conferred high binding affinity for mu receptor ligands including morphine and [D-Ala2,N-methyl-Phe4,Gly5-ol]-enkephalin and low affinity for delta and kappa preferring ligands. Treatment of these cell lines with morphine and other mu agonists inhibited forskolin-induced cAMP accumulation, demonstrating a functional coupling of mMOR to the inhibition of adenylate cyclase. The predicted amino acid sequence of mMOR shares approximately 55% overall amino acid identity with the delta receptor and approximately 97% identity with the recently reported rat mu opioid receptor. Expression of the mu receptor in mouse brain as revealed by in situ hybridization parallels the reported pattern of distribution of mu-selective ligand binding sites. Chromosomal localization (to mouse chromosome 10) and Southern analysis are consistent with a single mu opioid receptor gene in the mouse genome, suggesting that the various pharmacologically distinct forms of the mu receptor arise from alternative splicing, post-translational events, or from a highly divergent gene(s).

Amino Acid Sequence↗

Short course of ofloxacin for treatment of multidrug-resistant typhoid.

In recent years, multiresistant strains of Salmonella typhi have emerged in many tropical countries. These strains remain highly sensitive to the fluoroquinolone antibiotics, although use of these drugs by children is considered contraindicated because of their reported toxicity in the cartilage of experimental animals. In a paired, open, randomized study during an epidemic of multidrug-resistant typhoid in southern Vietnam, two short-course ofloxacin regimens (15 mg/kg daily for 3 days and 10 mg/kg daily for 5 days) were compared for the treatment of uncomplicated typhoid fever. Of 438 patients enrolled (of whom 286 were < or = 14 years old), 228 had blood cultures positive for Salmonella species (S. typhi, 207; S. paratyphi A, 19; and S. choleraesuis, 2). There was one treatment failure in a patient who took only one dose of ofloxacin. Otherwise, both regimens were completely effective; there were no proven carriers, and there was no evidence of toxicity, particularly in children. A 3-day course of ofloxacin proved to be safe and highly effective in the treatment of uncomplicated, multidrug-resistant typhoid fever.

Adolescent↗

von Willebrand factor and factor VIII in renal transplant recipients under immunosuppression with cyclosporine and steroids. Sequential measurements over 4 months in 17 patients.

In 17 consecutive cadaver kidney transplant recipients treated with cyclosporine (CsA) and steroids, the median of antigenic and functional levels of von Willebrand factor (vWF) and factor VIII (FVIII) before transplantation were elevated (vWF:Ag: 206%, vWF:RCof: 202%; FVIII:Ag: 248%, FVIII:C: 224%; normal values 50-150%). Sequential measurements after transplantation and during CsA treatment revealed a transient significant increase of median values with highest amounts of vWF:Ag of 362% (2 p less than 0.0001), FVIII:Ag of 398% (2 p less than 0.001) and FVIII:C of 360% (2 p less than 0.0001) (Friedman test). vWF:RCof did not show statistically significant changes. After 4 months, levels of vWF and FVIII comparable to those obtained before transplantation were observed. In univariate statistical analysis no correlation was found between vWF of FVIII on the one hand and plasma creatinine levels, CsA dose or CsA whole blood through levels on the other hand. However, multivariate statistics revealed to some extent a positive influence of CsA blood levels on vWF:Ag levels. Patients with vascular rejection or chronic CsA nephrotoxicity showed significantly lower levels of vWF:Ag as compared with patients without endothelial cell damage in the kidney (2 p less than 0.05). However, the difference in vWF:Ag levels already existed before transplantation. In contrast to recent reports, plasma vWF levels were not indicative of vascular injury in kidney graft recipients nor was the marked elevation of vWF and FVIII associated with thromboembolic complications ascribed to CsA treatment.

Cadaver↗

[Relationship between metabolic status and results of embryo collection in high-producing cows].

Blood samples were taken from 58 high-performance cows earmarked as donors for embryo transfer, one day before artificial insemination and following superovulation. An evaluation of 16 major indices showed the yield of transferable embryos to be clearly reduced by hypocholesterolemia, hyperproteinemia, and even more by hypophosphatemia. More than one deviating metabolic findings were obtained only from few animals which had the desired high number of embryos, that is above seven.

Animals↗

Epigenetic and genetic factors affect transgene methylation imprinting.

In some lines of transgenic mice, the methylation of MspI sites within or adjacent to the transgene locus is affected by the sex of the parent from which the transgene is inherited. These differences are consistent with a role for DNA methylation in genome imprinting. In a previous report, we noted that in one such line, all offspring of females exhibited hypermethylation of the transgene while only some offspring of males carried a hypomethylated transgene. In this report, we provide evidence that this phenomenon is controlled by at least two factors, one of which acts in cis and is dependent on the transgene locus, and one of which acts in trans and is supplied by the maternal genome. We also provide evidence that there are genetic differences between inbred mouse strains in the trans-acting factor.

Animals↗

Phenobarbital increases the theophylline requirement of premature infants being treated for apnea.

To determine the effect of phenobarbital sodium therapy and subependymal intraventricular hemorrhage (SEp-IVH) on the theophylline requirement of premature infants suffering with apnea and seizure activity, we compared three groups of patients as follows: group 1, those with apnea of prematurity (ten patients); group 2, those with apnea and SEp-IVH (ten patients); and group 3, those with apnea, SEp-IVH, and seizure activity for which they were receiving phenobarbital therapy (nine patients). Patients in groups 1 and 2 required lower dosages and blood levels of theophylline to control their apnea than did those in group 3, who required higher dosages and blood levels of methylxanthines. Theophylline dosages and blood levels did not significantly differ between groups 1 and 2. In group 3, the theophylline requirement for control of apnea was significantly increased after initiation of phenobarbital therapy. There seems to be a direct correlation between the increased requirement for theophylline and concomitant phenobarbital administration. The data suggest that phenobarbital increases theophylline requirement when treating neonatal apnea.

Apnea↗

Effect of protein malnutrition and maternal caffeine intake on the growth of fetal rat brain.

Pregnant dams were divided into two subgroups on day 10 of gestation. Half were fed a 20% protein diet and the other half an 8% protein diet. A second group also subdivided was pair-fed with rats of the first group. Their diet was supplemented with caffeine in amount calculated to provide daily doses of 2 mg/100 g body weight. On days 18, 20, and 22 randomly selected dams were injected with 3H-thymidine intraperitoneally and 1.5 h later their fetuses were delivered surgically in order to determine the rate of DNA synthesis along the gestation. The rest of the fetuses were delivered surgically on day 22. Pups' brains were rapidly removed and DNA, RNA, protein and 3H-thymidine uptake were studied. Average body weights of the fetuses in the caffeine-supplemented control group were smaller than those of the noncaffeine group. Effects of caffeine that were similar in both diet groups included a decrease in brain DNA content and concentration and an increase in brain protein content and concentration. However, the percent decrease and increase, respectively, was different depending on the nutritional status. DNA synthesis was not affected by malnutrition or caffeine supplementation on day 18 of gestation. Caffeine's effect on the rate of DNA synthesis was different on day 20 of gestation depending on nutritional status. Caffeine supplementation resulted in a decrease in DNA synthesis in both groups on day 22 of gestation. These data indicate that caffeine intake during pregnancy produces differential effects on fetal rat brain depending on dietary protein content.

Animals↗

Heparin cofactor II: purification and antibody production.

Heparin cofactor II (HCII) was purified from plasma to homogeneity. The procedure includes adsorption with (A1)OH3, fractionation with polyethylene glycol 6000, chromatography on QAE-Sephadex A-50, on heparin-Sepharose 4B and on Sephadex G-150. QAE-Sephadex A-50 chromatography provides a good separation of HCII from antithrombin III (AT) and most contaminants having a heparin affinity similar to that of HCII. HCII is eluted at 0.28 M NaCl from the heparin-Sepharose column. After gel filtration on G-150, contaminating AT was removed by immunoadsorption. Purified HCII shows an apparent Mr of 66,500 daltons as analyzed on SDS-polyacrylamide gel and 62,100 daltons by ultracentrifugation. Antibodies to HCII were raised in rabbits. Former antisera mostly directed to a contaminating protein were used to remove it from the HCII preparation. Antibodies to HCII were made monospecific by immunoadsorption on HCII-free plasma linked to Sepharose 4B. Since many functional AT assays have neglected the presence of HCII in plasma, antibodies to HCII using as immunoadsorbent will provide a more specific test for AT.

Antibody Specificity↗

Antithrombin III Basel. Identification of a Pro-Leu substitution in a hereditary abnormal antithrombin with impaired heparin cofactor activity.

Antithrombin III Basel is a hereditary abnormal antithrombin with normal progressive inhibition activity (normal reactive site) and reduced heparin cofactor activity (impaired heparin binding site). Structures of antithrombin III Basel and normal antithrombin III isolated from the same patient were compared by peptide mapping using the dimethylaminoazobenzene isothiocyanate precolumn derivatization technique. Of the approximately 50 tryptic peptides of normal and abnormal antithrombin III, one peptide comprising residues 40-46 had a different retention time in reversed-phase high performance liquid chromatography. The amino acid sequence of the peptide from antithrombin III Basel had a single substitution of Pro (normal) by Leu (abnormal) at position 41. This substitution is close to an Arg (residue 47) and a Trp (residue 49) which have previously been shown to be critical for heparin binding by antithrombin III. Although additional amino acid substitutions in antithrombin III Basel cannot be ruled out, this Pro-Leu replacement could cause a conformational change by increasing both the helical structure and the hydrophobicity around residue 41. These data suggest that: (i) the heparin binding site of antithrombin III encompasses the region containing residues 41, 47, and 49; and (ii) the impaired heparin cofactor activity of antithrombin III Basel is likely due to a conformational change of the heparin binding site induced by the Pro-Leu substitution at position 41.

Amino Acid Sequence↗

Association of hereditary heparin co-factor II deficiency with thrombosis.

A family was investigated for heparin co-factor II deficiency. Three of the five members examined had had thrombosis and their levels of heparin co-factor II were reduced to 50%. All five members had antithrombin III levels within the normal range. Analysis on crossed immunoelectrophoresis showed no qualitative abnormality of patient heparin co-factor II antigen. Since heparin co-factor II activity and concentration were reduced to the same extent, the deficiency was due to reduced protein synthesis.

Adult↗

Methodology and clinical significance of heparin cofactor II. Probable heparin cofactor II deficiency in a patient with cerebrovascular thrombosis.

HC II was functionally determined by thrombin inhibition in the presence of heparin in AT III-free plasma prepared by immunoadsorption on anti-AT III-Sepharose 4B column. HC II antigen concentration was assayed using specific antibodies to HC II. Simultaneously, AT III was measured. Plasma levels of HC II and AT III were determined in 110 patients with thrombotic tendency and two patients with obstetric complications and DIC. Highly significant correlations between activity and antigen prove the suitability of the methods. Reduced levels of HC II to about 50% with normal AT III values were repeatedly found in one patient with thrombotic tendency. The course of AT III and HC II during the process of DIC suggests that HC II may function as a thrombin inhibitor reserve when AT III becomes subnormally low.

Antithrombins↗

Purification of antithrombin 'Vicenza': a molecule with normal heparin affinity and impaired reactivity to thrombin.

Antithrombin III (AT) 'Vicenza', a previously described dysfunctional AT associated with familial thrombosis, has been isolated by heparin affinity chromatography. The purified molecule has been investigated by SDS-polyacrylamide gel electrophoresis and crossed immunoelectrophoresis after incubation with different amounts of thrombin. A normal affinity for heparin has been demonstrated. However, evidence is produced that AT 'Vicenza' poorly inhibits thrombin. Present data suggest that AT 'Vicenza' consists of a population of two molecules, half of which does not form a complex with thrombin however and loses its heparin affinity upon thrombin treatment.

Antithrombin III↗

Fifteen coagulation and fibrinolysis parameters in diabetes mellitus and in patients with vasculopathy.

Fifteen haemostasis parameters have been measured in 48 normal persons, 36 diabetic without and 44 with complications and 27 with peripheral arterial disease. Since the patient groups are older than normals, part of the differences are due to age. However, the differences are significant between normals and patients. They become highly significant for the diabetics with complications and nephropathy (Table 7). In diabetics without complications factor VIII functions, fibrinogen and thrombin time are related to age whereas there is a negative correlation for the fibrinolytic activity and antithrombin III. The diabetic complications shade off the correlations, which subsist only for VIIIR:CoF, VIIIR:Ag, ATIII and lysis before stasis. With Hbalc as dependent variable VIIIR:CoF is the only significant predictor variable in diabetics (Table 9).

Adult↗

Heparin cofactor II determination--levels in normals and patients with hereditary antithrombin III deficiency and disseminated intravascular coagulation.

A technique is described to completely remove antithrombin III (AT) from small amounts of human plasma by immunoaffinity chromatography on antibodies against human AT linked to Sepharose 4B. The level of heparin cofactor II (HCII) was not affected by the immunoadsorption. HCII activity was then determined by measuring the rate of human thrombin inhibition by 3 ways: a) activation with heparin in AT-free plasma, b) activation with dermatan sulfate in normal plasma and c) activation with dermatan sulfate in AT-free plasma. The normal range of HCII varied between 0.7-1.5 U/ml, as compared to a normal plasma pool containing by definition 1 U/ml. Highly significant correlations between assays as obtained from 40 normal plasmas proved the suitability of the 3 assays, although the progressive thrombin inhibition by AT, when not removed, contributed about one fifth to the thrombin inhibition by HCII in the presence of dermatan sulfate. There were also highly significant correlations between HCII activity and antigen, as determined by rocket immunoelectrophoresis using specific antibodies against HCII. Levels of HCII and AT were examined in 7 patients with hereditary AT deficiency and 7 patients with disseminated intravascular coagulation (DIC). In hereditary AT deficiency, whereas the AT activity was reduced by half, levels of HCII activity and antigen were in the normal range. In DIC, a parallel decrease of HCII and AT suggests that HCII may participate in the inhibition of thrombin released during DIC and thus provides an inhibitor reserve, once the AT level becomes subnormally low.

Antigens↗