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Biomedical subjects

L T Wong

Publications and source records attributed to L T Wong.

At least 37 records · Page 2Linked to original sources
PubMed1993

Pseudomonas aeruginosa colonization of the gastrointestinal tract in patients with cystic fibrosis.

Respiratory and fecal specimens from 111 patients with cystic fibrosis (CF) were cultured on 394 occasions to determine which site Pseudomonas aeruginosa colonizes first. By an enrichment and selection culture technique, P. aeruginosa was recovered from fecal cultures in 21 (42%) of 50 respiratory tract-positive patients but from only 3 (6.3%) of 48 respiratory tract-negative patients and from 1 (2.2%) of 45 control subjects. In 4 (22%) of the 18 patients who became culture-positive during the study, P. aeruginosa was recovered from a fecal specimen before respiratory colonization. Only 1 of these 4 became persistently colonized with P. aeruginosa in the respiratory tract; however, the serotype of the respiratory isolate was different from that of the fecal isolate. P. aeruginosa is recovered rarely from the feces of patients with CF who are culture-negative in the respiratory tract. In patients with CF, primary colonization with P. aeruginosa probably occurs in the respiratory tract.

Adolescent↗
PubMed1993

Systemic hemodynamic and hepatic microvascular responses to a 33% blood volume exchange with whole blood, stroma-free hemoglobin, and oxypolyhemoglobin solutions.

Little is known about the microvascular effects of blood replacement solutions. This study was undertaken to develop an animal model suitable for studies of the microcirculatory effects of such solutions and to investigate microvascular responses to isovolemic transfusion with stroma-free hemoglobin (SFH), whole donor blood, or a new potential blood substitute solution containing oxypolyhemoglobin (OPH) as an oxygen carrier. Hamster livers were exposed and the microcirculation studied using intravital epifluorescent video microscopy. 33% blood volume replacement with SFH elevated systemic blood pressure by 25 Torr. Accompanying this increase in pressure was a 36% decrease in sinusoidal blood flow velocity and a 10% decrease in terminal hepatic venular diameters. Terminal portal venular diameters did not change. Decrease in liver sinusoidal perfusion was not due to neutrophil mediated injury, as myeloperoxidase activity in jejunum, liver, kidney, and lung remained unchanged. The reduction in perfusion was likely due to systemic vasoconstriction produced by SFH. In contrast, transfusion with whole blood did not change any of the measured parameters showing the excellent stability of the model. OPH transfused animals exhibited only a small 10 Torr transient increase in MAP 15 min post-transfusion. By 30 min MAP returned to the pre-infusion value. No significant changes were observed in either venular diameters or sinusoidal velocities in this group of animals. These results demonstrate suitability of this model for studies of the microcirculatory and hemodynamic effects of blood replacement solutions. Furthermore, OPH solution produced only minor transient disturbances in microvascular and systemic parameters.

Animals↗
PubMed1993

Barrett's esophagus in children with cystic fibrosis: not a coincidental association.

Barrett's esophagus (BE) is a premalignant condition, and a recognized complication of severe gastroesophageal (GE) reflux. Children with cystic fibrosis (CF) have a marked predilection to develop GE reflux, but Barrett's esophagus is one complication of GE reflux not previously described in CF. We describe in detail two adolescents with CF who were found to have Barrett's esophagus, and mention three other cases. The presence of Barrett's esophagus in CF patients may be missed because GE reflux is often relatively silent in CF, because patients may consider mild upper gastrointestinal (GI) symptoms as "part of CF," and because of the nature of Barrett's epithelium itself. Upper gastrointestinal (GI) endoscopy with documentation of landmarks and multiple targeted biopsies should be performed in children with CF with even mild symptoms of GE reflux or an abnormal 24 h intra-esophageal pH study. Any biopsies containing columnar epithelium should be stained with Alcian blue at pH 2.5 to look for goblet cell metaplasia, i.e., Barrett's esophagus. Children with CF may be a high-risk group for development of Barrett's esophagus and its complications, especially given the increased survival in CF.

Adolescent↗
PubMed1993

Gender-associated differences in rat renal tubular amantadine transport and absence of stereoselective transport inhibition by quinine and quinidine in distal tubules.

The present studies compared male and female rat renal proximal and distal tubular uptake of amantadine, in relation to their transport kinetics and enantioselective inhibition by two diastereoisomers, 8S,9R-(-)-quinine and 8R,9S-(+)-quinidine. Under control conditions, amantadine was concentrated by both tubule fractions with a gender difference for distal tubules (tissue:medium ratio, 18.0 +/- 1.4 for males and 11.0 +/- 0.6 for females; mean +/- S.E.M., P < .05). This was reflected by a higher Km value only in female distal vs. proximal tubular tissue (153 +/- 8 vs. 108 +/- 9 microM; P < .01) but decrease in Vmax values in distal compared to proximal tubules (P < .01) showed no gender-related difference. In proximal tubules, 8S,9R-(-)-quinine and 8R,9S-(+)-quinidine competitively inhibited amantadine transport with apparent inhibitory potency of 2- to 3-fold in favor of 8S,9R-(-)-quinine (P < .01) and without gender preference. Conversely in distal tubules, competitive inhibition of amantadine transport was also elicited by either 8S,9R-(-)-quinine or 8R,9S-(+)-quinidine at a similar concentration range (10-1000 microM), with absence of chiral or gender preference. The present transport data have demonstrated an apparent absence of stereoselectivity in distal tubular uptake inhibition of amantadine, and are suggestive of disparate pathways and/or rate limiting steps involved between renal proximal and distal tubular handling of chiral organic cations for both genders, and between genders for distal tubular transport of amantadine.

Amantadine↗
PubMed1992

Stereoselective inhibition of renal organic cation transport in human kidney.

Amantadine was found to be concentrated by human cortical slices, with apparent Km and Vmax values of 187 +/- 11 microM and 1.37 +/- 0.28 nmol mg-1 min-1 respectively (mean +/- s.e. mean, n = 4). Addition of quinine (8S, 9R-(-)-isomer) or quinidine (8R, 9S-(+)-isomer) competitively inhibited this accumulation (apparent Ki values of 261 +/- 44 (n = 4) and 586 +/- 68 microM (n = 3), respectively). The stereoselectivity of this inhibition is the reverse of that seen with respect to the renal clearances of the diastereoisomers.

Adult↗
PubMed1992

Pharmacokinetic studies in the rat on a o-raffinose polymerized human hemoglobin.

We have studied the plasma half-life (T 1/2), oxygen-binding affinity (P50), organ distribution, and excretion of the individual molecular weight (MW) components of human hemoglobin polymerized with periodate-oxidized, ring-opened raffinose (oR poly-Hb), following transfusion in the rat. The model was an isovolemic 50% exchange transfusion in the conscious, chronically catheterized rat. Total plasma Hb levels yielded a (T 1/2) of 10 to 11 hr for oR poly-Hb. The T 1/2 values of individual MW components of the poly-Hb as determined by size-exclusion HPLC were approximately: 4 hr for the monomeric fraction (Hb)1, 9 hr for the dimer (Hb)2, and 15 hr for the fraction representing trimers to nanomers (Hb)3-9. The P50 values of plasma samples containing oR poly-Hb (collected from 0-24 hr after exchange) remained unchanged at 28 +/- 3 mmHg. oR stabilized and polymerized Hb were not excreted via the kidneys. Hepatic and renal distribution as well as plasma and renal clearance were determined by liquid scintillation counting using individual tritium [3H] labelled MW components purified from [3H]-oR poly-Hb: (Hb)1/2, (Hb)1, (Hb)2, (Hb)3&4, and (Hb) greater than 9. In kidney, uptake (determined by the relative concentration of radioactivity) decreased with increasing MW of the labelled component. Conversely, in liver, uptake increased with increasing MW. Plasma and renal clearance results were consistent with those obtained by HPLC analysis. Hematocrit levels returned from a 20% post-transfusion level to normal pre-transfusion levels (44%) within 10 days after the exchange.

Animals↗
PubMed1992

Interference with renal organic cation transport by (-)- and (+)-nicotine at concentrations documented in plasma of habitual tobacco smokers.

Nicotine is the principal psychoactive Nicotiana alkaloid in tobacco. In the present study, we used amantadine as a marker and investigated the potential ability of nicotine and cotinine to interfere with renal organic cation transport in vitro. [3H]Amantadine is concentrated actively by isolated proximal tubules, distal tubules and cortical slices. In proximal tubules, the addition of (-)- or (+)-nicotine (0.1-100 microM) facilitated amantadine (10 microM) accumulation. Apparent Km for amantadine uptake was decreased by a clinically relevant concentration of (-)- and (+)-nicotine (0.4 microM), from 78 +/- 2 to 52 +/- 2 and 61 +/- 5 microM, respectively (mean +/- S.E.M., P less than .05), whereas Vmax was not altered (6.6 +/- 0.1 to 6.3 +/- 0.1 and 6.5 +/- 0.2 nmol/mg/min). The addition of (-)-cotinine (0.4-100 microM) also facilitated amantadine uptake, but with lesser efficacy. Possible mechanisms underlying the present enhancement of uptake include facilitation of amantadine influx and/or attenuation of efflux. Efflux data indicate a prominent hindrance of amantadine egress from preloaded tubules in the presence of 0.4 microM (-)- and (+)-nicotine (51 +/- 4 to 32 +/- 8 and 27 +/- 4 pmol/mg/30 sec, P less than .05) and are supportive of the latter notion. In distal tubules, (-)- or (+)-nicotine produced inhibition only a high concentrations (greater than or equal to 100 microM). Km was increased by 400 microM (-)- and (+)-nicotine from 76 +/- 5 to 124 +/- 9 and 116 +/- 17 microM, and Vmax was moderately decreased from 3.4 +/- 0.5 to 3.0 +/- 0.4 and 3.0 +/- 0.4 nmol/mg/min (P less than .05). The incorporation of (-)-cotinine did not alter amantadine uptake. Enhancement of uptake by (-)- or (+)-nicotine was absent in cortical slices, in which tubular luminal transport has ben proposed to be insignificant, and only low affinity inhibition was apparent. The present data indicate potent interference of renal proximal tubular transport of amantadine by nicotine at concentrations equivalent to those documented in plasma of habitual tobacco smokers and suggest potential alterations in renal organic cationic drug elimination in these subjects.

Amantadine↗
PubMed1991

Hepatic dysfunction in Alström disease.

Alström disease is a rare disorder; less than 20 cases have been reported. An 11-year-old girl is described with this condition. She has pigmentary retinopathy, sensory neural deafness, obesity, Type II diabetes mellitus, hyperlipidemia, and acanthosis nigricans. However, in addition she developed hepatic dysfunction, pathologically similar to chronic active hepatitis. This may be a further, previously undescribed systemic manifestation of Alström disease.

Acanthosis Nigricans↗
PubMed1991

Differential effects of histamine H2 receptor antagonists on amantadine uptake in the rat renal cortical slice, isolated proximal tubule and distal tubule.

The interaction between amantadine and two histamine receptor antagonists was examined in the rat kidney. Amantadine (10 microM, 30 sec) was actively accumulated by cortical slices (slice/medium ratio = 0.4 +/- 0.3 [3.3 +/- 0.3 at 4 min], mean +/- S.E.M.), isolated proximal tubules (tubule/medium ratio = 35 +/- 1) and distal tubules (tubule/medium ratio = 19 +/- 2). In cortical slices, low cimetidine concentrations facilitated amantadine accumulation, whereas higher concentrations produced inhibition. Uptake in proximal tubules was enhanced by cimetidine and reached a maximum at approximately 100 microM. Cimetidine (20 microM) decreased the apparent Km (88 +/- 5 to 55 +/- 3 microM, P less than .005) without altering Vmax (6.8 +/- 0.5 to 5.8 +/- 0.6 nmol/mg/min). Conversely, cimetidine did not enhance uptake in distal tubules but elicited competitive inhibition at concentrations greater than 1 mM. Although this may partially delineate the differences observed between the cortical slice and proximal tubule data, such a discrepancy may also implicate additional sites of interaction in other segments of the cortical nephron and/or cimetidine inhibition of the relatively more significant luminal amantadine efflux in the proximal tubules. Ranitidine did not enhance amantadine accumulation but produced inhibition at high concentrations. In proximal and distal tubule preparations, ranitidine (10 mM) increased Km from 86 +/- 7 to 121 +/- 8 and 95 +/- 5 to 160 +/- 10 microM, respectively (P less than .05), whereas Vmax was not changed (8.9 +/- 0.7 to 7.9 +/- 0.8 and 4.3 +/- 0.1 to 3.8 +/- 0.2 nmol/mg/min, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Amantadine↗
PubMed1990

Estrogen-binding properties of rat serum alpha 1-fetoprotein and its isoforms. Investigation of the apparent non-integrality of sites on the unfractionated protein.

Rat fetal serum alpha 1-fetoprotein (AFP), a heterogeneous glycoprotein, binds estrogens with high affinity but at a fractional number of sites even after treatment with charcoal (n = 0.6), which may mean 60% of the protein has 1 site and the remainder none. To investigate the origin of this fractional number of sites the "native" protein (purified by negative affinity chromatography) was further purified (step 1) and fractionated (step 2) into its two main charge variants (electrophoretically "slow" and "fast") by a two-step fast-protein liquid chromatography method. The binding parameters for estrone and estradiol-17 beta of the "native" and "repurified" proteins and of each charge variant were determined by equilibrium microdialysis. The molar extinction coefficient at 278 nm of each sample was also determined. (1) The "repurified" AFP and each charge variant had a number of binding sites for estrogens close to unity. This increase in the number of sites could neither be explained by the loss of a non-binding isoform (corresponding to 40% of the protein) during chromatography, nor by the existence of complex negative modulatory interactions between isoforms. (2) The affinities for estrogens of the "repurified" protein and the two charge variants were slightly decreased compared to that of "native" AFP, except that the "fast" form had the "native" protein's high affinity for estrone--but not for estradiol-17 beta. (3) The molar extinction coefficients at 278 nm of the "repurified" AFP and the isoforms were much lower than that of the "native" protein. These results suggest that the presence of (an) inhibitor(s) of estrogen binding on the "native" protein which is/are removed by the ion-exchange fast protein liquid chromatography (FPLC) column. A ligand absorbing at 278 nm, which may or may not be the inhibitor, is also removed. The isoform heterogeneity with respect to estrone binding is discussed.

Animals↗
PubMed1990

Biochemical investigation of a child with molybdenum cofactor deficiency.

A girl aged eight months, who presented with developmental delay and dislocated optic lenses, was diagnosed as having combined sulfite oxidase and xanthine dehydrogenase deficiencies consistent with molybdenum cofactor deficiency. The diagnosis was confirmed by demonstrating the absence in urine of urothione, a molybdenum cofactor metabolite. Prenatal diagnosis excluded the disease in the mother's second pregnancy. A summary of an in vitro study of molybdenum cofactor synthesis in the patient is given.

Coenzymes↗
PubMed1990

The high incidence of valproate hepatotoxicity in infants may relate to familial metabolic defects.

The incidence of fatal hepatic failure associated with valproic acid (VPA) therapy is highest in children under the age of three years, particularly in those with developmental delay. The pathogenesis of VPA hepatotoxicity is unclear but may relate to the accumulation of a toxic metabolite of VPA which impairs fatty-acid oxidation. We describe two unrelated infants with developmental delay who developed hepatic failure while receiving VPA. Siblings of both children subsequently developed hepatic steatosis and intractable seizures without being exposed to VPA. This suggests that the two children who developed liver failure when receiving VPA may have had a familial metabolic disorder. Familial metabolic disorders may account partly for the higher incidence of fatal hepatotoxicity described in infants receiving VPA.

Chemical and Drug Induced Liver Injury↗
PubMed1990

Cardiomyopathy associated with nonendemic selenium deficiency in a Caucasian adolescent.

We describe a girl aged 17 y who died after a cardiac arrest secondary to septic shock. At autopsy, the enlarged, soft, and flabby heart showed microscopic evidence of acute myocardial infarction, myocardial edema, myocardiocyte loss, replacement fibrosis in the interventricular septum, and right and left ventricular hypertrophic nucleomegaly. The pathological diagnosis was that of cardiomyopathy due to prolonged selenium deficiency. The patient had been on total parenteral nutrition for 17 mo, following extensive bowel resection for intractable pain, nausea, and vomiting caused by chronic idiopathic intestinal pseudoobstruction. Seven months before death, when severe biochemical selenium deficiency was diagnosed, supplemental selenium was added to the infusion, and plasma selenium concentrations increased. In long-standing selenium deficiency, sepsis may contribute the final insult to a damaged myocardium, triggering symptomatic cardiac failure and sudden death.

Adolescent↗
PubMed1990

Stereoselective inhibition of amantadine accumulation by quinine and quinidine in rat renal proximal tubules and cortical slices.

The renal organic cation transport system was examined. The accumulation of a nonchiral cation, amantadine, by rat renal proximal tubules and cortical slices was investigated, together with the effects of two diastereoisomers, quinine and quinidine. The proximal tubules actively concentrated amantadine with a tissue/medium ratio of 96.3 +/- 1.7 (mean +/- S.E.M., n = 18). Apparent Km was 85 +/- 2 microM and Vmax was 8.0 +/- 0.2 nmol/mg of tubular protein per min. Amantadine accumulation was inhibited competitively by quinine and quinidine with Ki values of 32 +/- 3 and 84 +/- 11 microM, respectively (n = 4). Amantadine was also concentrated by renal cortical slices with tissue/medium ratio of 3.3 +/- 0.3 (n = 4). Apparent Km and Vmax were 94.0 +/- 5.2 microM and 1.27 +/- 0.08 nmol/mg of tubular protein per min, respectively (n = 10). Quinine and quinidine again inhibited amantadine accumulation competitively by the slices, with Ki values of 368 +/- 28 and 780 +/- 84 microM, respectively (n = 4). A similar affinity (Km) for amantadine was observed in both preparations. However, the lower Vmax value in the slice system may be due to additional amantadine transport sites with lower capacity, lesser luminal accumulation and/or limited substrate(s) penetration in the cortical slices. In either preparation, quinine and quinidine functioned as competitive inhibitors and stereoselectivity was observed for the (-)-isomer, quinine, over the (+)-isomer, quinidine. Additional transport sites, reduced luminal substrate accumulation and/or diffusional restraints in the slices are also feasible mechanisms in explaining the differences in Ki values between the two preparations, and their relative contributions await further investigation.

Amantadine↗
PubMed1988

Follow-up of men in the recovery period immediately after the cessation of gossypol treatment.

Variables in 46 men who had stopped taking gossypol in two centres in China were investigated for their predictive association with the degree and time of recovery of spermatogenesis. Thirty-nine (87%) were azoospermic at cessation of gossypol treatment. In those with sperm present the geometric mean concentration and total sperm count were 8.3 x 10(6)/ml and 30.7 x 10(6), respectively. Twenty-eight (61%) recovered to a defined threshold spermatogenic function (sperm concentration greater than or equal to 20 x 10(6)/ml), with median recovery time 1.1 years. However, 18 men (39%) had not recovered after a median follow-up of 1.9 years and, of these, 10 (22%) remained azoospermic. The failure of recovery was strongly associated with longer treatment, greater total dose of gossypol, smaller testicular volume, elevated FSH concentrations and, to a lesser extent, with greater body weight.

Contraceptive Agents, Male↗