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Biomedical subjects

F Fan

Publications and source records attributed to F Fan.

72 records · Page 4Linked to original sources
PubMed1996

[Evaluation of the manifestations of bronchial lesions on ligular segments in clinical and pathological aspects].

OBJECTIVE: To evaluate the characteristic findings of lesions on lingular bronchus. METHODS: All cases examined by fiberoptic bronchoscopy and (or) bronchial biopsy, during the period of 1979-1994, 4,300 in total, were evaluated retrospectively. RESULTS: Abnormal lesions were found in 173 cases (4%), among them, bronchogenic carcinoma was pathologically documented in 106 cases (61.3%). The incidence of cancer in lingular segment was much higher than that in right middle lobe, in which 34 (28.3%) of 120 cases were proved. CONCLUSIONS: Paying special attention to look for the definite diagnosis on the bronchial lesions was suggested since it is important for early diagnosing malignant illness, and the value of bronchoscopy was also highlighted by the authors.

Adult↗
PubMed1995

Effect of pH on the conformation and backbone dynamics of a 27-residue peptide in trifluoroethanol. An NMR and CD Study.

The C-terminal fragment, residues 385-411, from human fibrinogen gamma-chain, i.e. KIIPFNRLTIGEGQQHHLG-GAKQAGDV, shows multiple turn conformations in aqueous solution (Mayo, K. H., Burke, C., Lindon, J. N., and Kloczewiak, M. (1990) Biochemistry 29, 3277-3286). The present study investigates the effect of pH and trifluoroethanol on the conformation and backbone dynamics of this 27-residue peptide. Both circular dichroism (CD) and 1H-NMR data indicate the normally observed increased helical conformations as a function of increasing trifluoroethanol. 1H-NMR structural studies done in the presence of 40% trifluoroethanol, pH 5.3, yield a network of nuclear Overhauser effects consistent with significant populations of helix-like conformation. Distance geometry calculations based on nuclear Overhauser effect-derived distance constraints yield a family of structures with relatively well defined N- and C-terminal conformations and an ill defined mid-peptide region from Gly397 to Gly403. Similar conformational populations are observed at pH 2.5. CD studies, however, indicate an increase in average alpha-helix content on decreasing the pH from 6 to 2. This apparent conflict between CD and NMR results may be explained by a transition from multiple beta-turn character at pH 5.3 to increased alpha-helix structure at pH 2.5. 13C alpha NMR relaxation data analyzed with the Lipari-Szabo model-free approach provide order parameters that demonstrate little if any influence of pH on backbone motional restrictions within the more flexible mid-peptide domain. At low pH, however, motions become less restricted within N-terminal residues Lys385-Phe389 and more restricted within C-terminal residues Ala405-Val411.

Amino Acid Sequence↗
PubMed1995

Design and evaluation of nonpeptide fibrinogen gamma-chain based GPIIb/IIIa antagonists.

Two series of nonpeptide turn mimetics were designed by analysis of the solution NMR structure of the 385-411 sequence of the gamma-chain of fibrinogen. These compounds, based on the KQAGD (Lys-Gln-Ala-Gly-Asp, 406-410) sequence, were synthesized and studied in vitro. The most interesting compound from our study, RWJ 50042 (25), exhibits potent inhibition of fibrinogen binding to GPIIb/IIIa (IC50 = 0.009 microM), as well as thrombin- or collagen-induced platelet aggregation (IC50 = 0.76, 0.14 microM). Since the 400-411 sequence is required for gamma-chain bioactivity and is a unique recognition sequence among ligands for integrins, vis-a-vis other RGD (Arg-Gly-Asp)-presenting proteins, these turn mimetics may represent a new, selective approach to antagonism of the fibrinogen receptor.

Amino Acid Sequence↗
PubMed1995

Substitutions of isoleucine residues at the adenine binding site activate horse liver alcohol dehydrogenase.

The contributions of isoleucine residues 224 and 269 of horse liver alcohol dehydrogenase to binding of the adenine moiety of NAD and to catalysis were studied by replacing Ile-224 with glycine (I224G) and Ile-269 with serine (I269S). The kinetic mechanisms of wild-type and both mutated liver enzymes were ordered. Affinities for several adenosine derivatives were decreased 5-50-fold by both substitutions. The I269S mutation differentially destabilized binding of the complete coenzyme, as affinities for NAD+ and NADH were decreased about 60-fold with the I224G enzyme and 350-fold for the I269S enzyme. The I269S substitution increased the rate constants for the conformational change that occurs when NAD+ binds. The maximum velocities for ethanol oxidation increased 7-fold with the I224G enzyme and 26-fold with the I269S enzyme due to the faster release of NADH. Hydride transfer limits the rate of oxidation of ethanol by the I269S enzyme. Inhibition constants for the substrate analogues, 2,2,2-trifluoroethanol and N-methylformamide, and catalytic efficiencies (V/Km) for ethanol and acetaldehyde were not changed by the mutations, indicating that binding of the adenosine moiety of the coenzyme is not necessarily coupled to the subsequent reaction of substrates.

Adenine↗
PubMed1995

Short- and long-term biochemical effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin in female Long-Evans rats.

The aim of this study was to examine short- and long-term biochemical effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in female Long-Evans (L-E) rats. In the short-term study, female rats were dosed orally with 5.3, 12, 18 and 60 micrograms TCDD/kg and sacrificed 4 days after dosing. In the long-term study, rats were dosed with 27, 40 and 60 micrograms TCDD/kg and sacrificed 90 days after dosing. Four days after dosing, ethoxyresorufin O-deethylase (EROD) activity was fully induced at all doses studied, hepatic phosphoenolpyruvate carboxykinase (PEPCK) and gamma-glutamyl transpeptidase (gamma-GT) activities were dose-dependently reduced, whereas hepatic tryptophan 2,3-dioxygenase (TdO) activity was stimulated at low doses but decreased at high doses. Serum total T4 (TT4) levels were dose-dependently decreased, whereas serum total T3 (TT3) and tryptophan levels were unaffected. The short-term effects of TCDD examined in this study indicate only small differences in the response of female L-E rats to TCDD as compared to males. Ninety days after dosing, liver EROD activity revealed considerable reversibility although it was still elevated compared to controls. Hepatic PEPCK activity at this time point was no more different from controls. In contrast to 4 days after dosing, serum TT3, TT4 and hepatic gamma-GT activity were dose-dependently elevated at the 90-day time point. These findings have significant implications for the interpretations of subchronic and chronic effects of TCDD on thyroid homeostasis and on the formation of preneoplastic liver foci.

Animals↗
PubMed1995

[Observations of blood circulation disturbance in random skin flap].

Thirty-nine rats were used to study the mechanism of random flap necrosis. A random flap (3 cm x 9 cm) created on the back of each rat was observed with naked eye, microscope, skin thermometer and laser Doppler flowmeter. The average surviving length of the flap was 4.69 +/- 0.47 cm. We found that the following observations indicated circulation disturbance in the "shock flap": After surgery, the color of the flap became dark; skin temperature kept falling; when the room temperature was about 20 degrees C, the flap temperature was below 28.5-29.0 degrees C; at one hour postoperation, LDF value decreased more than 50%; microcirculation of the flap stagnated without recovery. We conclude that necrosis of the flap can be fully predicted.

Animals↗
PubMed1994

Relationship between acute toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and disturbance of intermediary metabolism in the Long-Evans rat.

The aim of this study was to examine the acute toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin, (TCDD) in a rat strain other than the Sprague-Dawley (S-D) rat, for which most of our data have been generated thus far. Doses for the biochemical study were selected based on an acute range-finding study, which indicated that Long-Evans (L-E) rats are somewhat less susceptible to TCDD toxicity than are S-D rats. Male L-E rats were dosed orally with 10, 20, 45, 67, 100 and 150 micrograms/kg TCDD. Body weight and feed intake were dose-dependently decreased prior to killing of the animals. Eight days after dosing, animals were killed and tryptophan, total T4 (TT4) and total T3 (TT3) levels were determined in serum, whereas the activities of ethoxy-resorufin-O-deethylase (EROD), phosphoenolpyruvate carboxykinase (PEPCK), gamma-glutamyl transpeptidase (gamma-GT) and tryptophan 2,3-dioxygenase (TdO) were measured in liver. EROD activity was fully induced at all doses studied, indicating that as in S-D rats, Ah-receptor-mediated effects do not seem to play any major role in the acute toxicity of TCDD in this rat strain either. Hepatic PEPCK activity was dose-dependently decreased in a similar dose range as in S-D rats, indicating inhibition of gluconeogenesis. Feed intake was dose-dependently decreased as a result of a dose-dependent elevation in serum tryptophan levels, which in turn were related to reduced liver TdO activity. Hepatic gamma-GT activity was also dose-dependently reduced.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Development of cross-tolerance between delta 9-tetrahydrocannabinol, CP 55,940 and WIN 55,212.

In previous studies it was shown that the structurally dissimilar compounds delta 9-THC, CP 55,940 and WIN 55,212 produced more or less the same pharmacological effects and interacted with the same cannabinoid receptor. However, their potencies vary across a number of pharmacological assays, suggesting that a single mechanism may not account for all of their actions. To further explore possible differences among these cannabinoids, cross-tolerance studies were conducted. Specifically, the ability of delta 9-THC, CP 55,940 and WIN 55,212 to produce hypoactivity, hypothermia, antinociception and catalepsy was assessed in mice that had been chronically treated with either delta 9-THC or CP 55,940. The results indicated the delta 9-THC-treated mice were tolerant to delta 9-THC. The degrees of tolerance were 15.9, 7.8, and 13.4 for spontaneous activity, hypothermia and antinociception, respectively. Mice chronically treated with delta 9-THC also exhibited tolerance to some of the behavioral effects of CP 55,940 and WIN 55,212. The tolerance induced by repetitive administration of CP 55,940 was substantial. The ED50 for CP 55,940 was shifted 102 fold for spontaneous activity, 100 for hypothermia and 44 for catalepsy. Also, some cross-tolerance to delta 9-THC and WIN 55,212 was observed in CP 55,940 chronically treated mice. These findings indicate that cross-tolerance develops between delta 9-THC, CP 55,940 and WIN 55,212 and that these agents have some actions in common. However, quantitative differences in their development of cross-tolerance suggests that all of their actions may not be identical.

Analgesics↗
PubMed1993

Development of behavioral tolerance to delta 9-THC without alteration of cannabinoid receptor binding or mRNA levels in whole brain.

The effect of repetitive administration of delta-9-tetrahydrocannabinol (delta 9-THC) in mice on behavioral and biochemical tolerance was determined in this study. Mice were injected twice daily with 10 mg/kg delta 9-THC for 6.5 days. On day 8, spontaneous activity was assessed or whole-brain homogenates were prepared for the cannabinoid receptor binding and mRNA studies. Although a twenty-sevenfold tolerance to delta 9-THC was observed in the behavioral assay, there was no significant alteration in receptor binding or mRNA levels.

Animals↗
PubMed1991

An aspartate residue in yeast alcohol dehydrogenase I determines the specificity for coenzyme.

In the three-dimensional structures of enzymes that bind NAD or FAD, there is an acidic residue that interacts with the 2'- and 3'-hydroxyl groups of the adenosine ribose of the coenzyme. The size and charge of the carboxylate might repel the binding of the 2'-phosphate group of NADP and explain the specificity for NAD. In the NAD-dependent alcohol dehydrogenases, Asp-223 (horse liver alcohol dehydrogenase sequence) appears to have this role. The homologous residue in yeast alcohol dehydrogenase I (residue 201 in the protein sequence) was substituted with Gly, and the D223G enzyme was expressed in yeast, purified, and characterized. The wild-type enzyme is specific for NAD. In contrast, the D223G enzyme bound and reduced NAD+ and NADP+ equally well, but, relative to wild-type enzyme, the dissociation constant for NAD+ was increased 17-fold, and the reactivity (V/K) on ethanol was decreased to 1%. Even though catalytic efficiency was reduced, yeast expressing the altered or wild-type enzyme grew at comparable rates, suggesting that equilibration of NAD and NADP pools is not lethal. Asp-223 participates in binding NAD and in excluding NADP, but it is not the only residue important for determining specificity for coenzyme.

Alcohol Dehydrogenase↗
PubMed1986

Monotherapy of mild hypertension with nifedipine.

The effectiveness of nifedipine as first-line monotherapy for mild diastolic hypertension (range: 95 to 105 mm Hg) was tested in this placebo-controlled, double-blind, randomized trial. Fifty-six patients were enrolled and, after titration of the placebo or active drug, they were followed for 12 weeks. Significant declines in the sitting systolic and diastolic pressures of -19 +/- 4 mm Hg (standard error) and -13 +/- 2 mm Hg, respectively, were observed during this follow-up period. Overall, 75 percent of patients receiving active drug had diastolic pressures less than or equal to 90 mm Hg at the last treatment visit. Heart rate was not significantly changed in the sitting position during the treatment period, and the majority of patients (75 percent) showed a response to nifedipine doses of 10 or 20 mg orally three times daily in the capsule form. The levels of the systolic and diastolic pressures at entry were not predictive of the dose of nifedipine required for effective blood pressure control.

Adult↗
PubMed1985

Role of exercise treadmill in diagnosing hypertension.

Using exercise treadmill testing (ETT), the authors undertook an evaluation of a patient who remained normotensive following termination of two-drug antihypertensive therapy. The hypertensive treadmill results suggest incomplete resolution of the hypertensive state and a potential role of the ETT in adding precision to the diagnosis of hypertension and monitoring control.

Adult↗
PubMed1984

Effects of arterial pressure on endothelial transport of macromolecules.

The effects of variations in transmural pressure over a range of 0 to 200 mmHg on transendothelial transport of macromolecules were studied in the canine common carotid artery. The uptake of 125I-albumin per unit artery weight increased with rising pressure. There was no significant difference in albumin permeability per unit luminal surface area between 0 and 100 mmHg, but permeability nearly doubled when pressure was raised to 200 mmHg. The contribution of an increased rate of transendothelial vesicle diffusion, as evaluated from the experimental determination of the ratio of attached-to-free vesicles and theoretical modeling, was found to be negligible. The reduction in transendothelial vesicle diffusion distance due to pressure-induced thinning of the peripheral zone contributes to a 25% increase in permeability. With the use of colloidal Ag and Au of various sizes, vesicle loading of particles with diameters greater than or equal to 15 nm was found to be severely restricted at transmural pressure less than or equal to 100 mmHg, but it was significantly enhanced at 200 mmHg, when particles as large as 25 nm became detectable in endothelial vesicles and subendothelial space. This hypertension-induced increase in macromolecular transport across the endothelium may cause an overloading of the arterial wall with low-density lipoproteins and play a significant role in atherogenesis.

Animals↗
PubMedDate not supplied

Immunomodulatory effect of 2,3,7,8-tetrachlorodibenzo-p-dioxin tested by the popliteal lymph node assay.

Drugs and other chemicals that have the potential to induce or exacerbate systemic autoimmune diseases in humans are of great concern. The aim of this study was to examine the immune-disregulating potential of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) by using the popliteal lymph node (PLN) assay. Chlorpromazine (CPZ) was used as a reference compound for 2 reasons: (a) CPZ is known to elicit a positive response in this assay, and (b) CPZ is a structural analogue of TCDD. Male Sprague-Dawley rats were injected subcutaneously with either TCDD or CPZ into the right hind footpad, whereas vehicle alone was injected into the contralateral footpad. Control rats were injected with vehicle in both hind footpads. Animals were sacrificed on day 7, and their PLNs were removed, weighed, and immersed in 10% formalin. The PLN weight index (the weight ratio of right PLN over left PLN) was significantly higher in both CPZ- and TCDD-treated rats than in controls. Histological examinations of PLNs in the CPZ- and TCDD-treated rats revealed similar morphological changes in both groups (e.g., mild follicular hyperplasia with no evidence of an acute inflammatory response). These results indicate that TCDD has the potential to induce or exacerbate autoimmune-like reactions. Results also suggest that drugs may be useful surrogates to study the mechanism of toxicity of environmental chemicals that cannot be administered to humans.

Adjuvants, Immunologic↗
PubMedDate not supplied

Preventive care in diabetes mellitus. Current practice in urban health-care system.

Early identification and treatment of complications of diabetes mellitus may reduce the severity of the complications. As part of a program to reduce these complications in the Denver Department of Health and Hospitals patient population, our study determined how frequently preventive care, e.g., fundoscopic examinations, referral to an ophthalmologist, foot examinations, and assessment of cardiovascular risk factors, was provided to diabetic patients. With the use of billing records to identify a large sample of diabetic patients, a chart review of 544 patients was conducted. During the study year, the mean +/- SE number of visits to primary-care clinics was 5.7 +/- 0.22, with 86.4% having at least one visit. Most diabetic patients were seen by primary-care physicians; only 9% received care in a specialized diabetes clinic. Despite frequent primary-care visits, most diabetic patients in this county health-care system did not have documentation of care to detect complications of diabetes mellitus, and referral services for detection and treatment of these complications were infrequently used. Moreover, among patients seen on greater than or equal to 10 occasions in a primary-care setting, preventive care was not provided to 30% of the patients. Preventive care does not appear to be a regular part of a primary-care visit for most of the diabetic patients in this study.

Colorado↗
PubMedDate not supplied

Endothelial survival factors as targets for antineoplastic therapy.

Angiogenesis is essential for the growth and metastasis of solid tumors. The angiogenic process includes not only development of new blood vessels but also maintenance of the existing vasculature. Recent studies have demonstrated that several factors induce angiogenesis and also function as endothelial cell survival factors. Vascular endothelial growth factor, a potent angiogenic factor, is an endothelial cell survival factor whose tyrosine kinase receptors are limited to endothelial cells. Members of the angiopoietin family also bind to an endothelial cell-specific tyrosine kinase receptor. Angiopoietin-1 has been shown to stabilize endothelial cell networks, whereas angiopoietin-2 is antagonistic to angiopoietin-1 and destabilizes endothelial cell networks. Pericytes contribute to endothelial cell stabilization by cell-cell contact, secretion of survival factors, or both. In addition, integrins may function as endothelial cell survival factors by numerous mechanisms after binding to the extracellular matrix. The effects of many endothelial cell survival factors act in concert with vascular endothelial growth factor to enhance this essential step in angiogenesis. Targeting any of the aforementioned mechanisms for endothelial cell survival may provide novel therapeutic antineoplastic strategies.

Angiogenesis Inhibitors↗