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T H Lin

Publications and source records attributed to T H Lin.

174 records · Page 10Linked to original sources
PubMedDate not supplied

Excessive breast self-examination among first-degree relatives of newly diagnosed breast cancer patients. High-Risk Breast Cancer Consortium.

First-degree relatives (FDRs) of women with breast cancer may have heightened anxiety about their personal risk for developing breast cancer. Breast self-examination (BSE) is an important component of risk surveillance for all women. In this study, the authors describe a subset of FDRs who appear to excessively (> or = once per day) perform BSE. These women, who constituted 8% of 1,053 FDRs in this study, were compared with women who did not examine excessively. The excessive self-examiners were older, more frequently African American, and less educated. They were more likely to have an affected daughter and > or = two FDRs with breast cancer. They were significantly more likely to think frequently about breast cancer and to report that such thoughts affected their mood. In a multivariate analysis, three variables had significant independent associations with excessive BSE practice: ethnicity (odds ratio [OR] = 2.3), perceived risk of breast cancer compared with women without a family history (OR = 2.9), and frequency of thoughts about breast cancer (OR = 5.5). The women who practice excessive BSE would benefit from enhanced educational efforts and screening for the presence of psychiatric problems such as anxiety and hypochondriasis.

Adult↗
PubMedDate not supplied

Classification of some active compounds and their inactive analogues using two three-dimensional molecular descriptors derived from computation of three-dimensional convex hulls for structures theoretically generated for them.

Two three-dimensional (3D) molecular descriptors are used to classify 73 protease inhibitors against the human immunodeficiency virus type 1 (HIV-1). X-ray structures of these HIV-1 protease bound inhibitors are used as templates to generate the most probable bioactive conformations of the inhibitors. A convex hull computation algorithm is applied to each structure generated. The frequency of atoms lying on the vertexes of each hull is counted. Vertexes of the same atomic charge state are then gathered together as a set of commonly exposed groups for all the structures generated. The first 3D descriptor is computed as the maximum molecular path length among any three distinct commonly exposed groups, while the second 3D one is computed as the maximum molecular path length among any three atoms of nonconvex hull vertexes. We find that the 73 HIV-1 protease inhibitors can be classified by the first 3D descriptor into two groups, which agrees with the result of visual classification using the activity data as a criterion for these compounds. The classification scheme is then used to classify a database of 427 active trypsin inhibitors and their inactive analogues. The structures of these compounds are generated theoretically from steps of energy minimization and molecular dynamics. Classification for all these compounds is performed using the SYBYL hierarchical clustering method on the first 3D descriptor and then the second 3D one computed. It is found that some inactive analogues are completely separated from the active inhibitors at the first stage of classification using the first 3D descriptor. Most of the highly active inhibitors are classified into a cluster at the second stage of classification using the second 3D descriptor. Finally, most of these highly active inhibitors are separated from all the accompanying inactive analogues in the cluster through a structural alignment process using a set of commonly exposed groups determined for them.

Algorithms↗
PubMedDate not supplied

Solution conformation of a peptide corresponding to residues 151-172 of HIV-1 integrase using NMR and CD spectroscopy.

The solution structure of a synthetic peptide corresponding to residues 151-172 of HIV-1 integrase has been determined by NMR and CD spectroscopy. Residues 151-172 of HIV-1 integrase were predicted to be an alpha-helix and to be responsible for the oligomerization of HIV-1 integrase. Two-dimensional 1H NMR and CD studies indicate that this synthetic peptide adopts an amphipathic alpha-helical conformation in TFE-containing solution. However, concentration-dependent CD studies reveal that this peptide motif does not form dimers or oligomers in solution as predicted. These results are in agreement with the crystal structure of the catalytic domain of HIV-1 integrase reported recently.

Amino Acid Sequence↗
PubMedDate not supplied

Species-dependent stereopharmacokinetics of MK-927, a potent carbonic anhydrase inhibitor.

MK-927 [5,6-dihydro-4H-4(isobutylamino)thieno(2,3-B)thiopyran-2-sul fonamide -7,7 dioxide], a potent carbonic anhydrase inhibitor, contains a chiral center and is a mixture of two forms, R-(-)- and S-(+)-enantiomer. The latter has recently been designated as MK-417. Following iv administration of each enantiomer (0.05 mg/kg), dogs, rabbits, and rats cleared the R-(-)-enantiomer more rapidly than the S-(+)-enantiomer. The elimination clearance of the R-(-)-enantiomer was 2.01 +/- 0.34, 30.0 +/- 2.1, and 53.6 +/- 6.4 ml/hr/kg for dogs, rabbits, and rats, respectively. The corresponding values for the S-(+)-isomer were 0.0380 +/- 0.008, 1.15 +/- 0.20, and 1.29 +/- 0.09 ml/hr/kg. The ratio of the clearance of the R-(-)-enantiomer to that of the S-(+)-isomer was approximately 53 for the dog, 42 for the rat, and 26 for the rabbit, indicating that the degree of stereoselectivity in elimination kinetics of MK-927 enantiomers was species-dependent. Binding of the enantiomers to erythrocytes, presumably carbonic anhydrase, was also stereoselective and species-dependent; the S-(+)-enantiomer was bound more strongly than the R-(-)-isomer in all species. For both enantiomers, binding to carbonic anhydrase was found to be more extensive in dogs than in other species studied. The elimination clearance of the enantiomers in all species was roughly related to their binding affinity, greater Kd1 values being associated with more rapid clearance. However, binding data alone cannot quantitatively explain the degree of the species-dependent stereoselectivity in the elimination kinetics; other factors may also contribute.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMedDate not supplied

Effect of serum from renal failure and cirrhotic patients on the blood-brain barrier permeability to DL-propranolol in rats.

Our previous studies using an in vivo tissue-sampling single-carotid injection method have shown that the transport of DL-propranolol into rat brain is inhibited by the serum from rats with uranyl nitrate-induced acute renal failure. The present studies were designed to examine the effect of serum from patients with renal or liver disease on the transport of DL-propranolol into the rat brain. While the binding of DL-propranolol to serum from cirrhotic patients was significantly decreased compared to normal serum, there was no change for the serum from patients with renal failure. In the carotid injection studies, the brain transport parameters such as the brain uptake index (BUI), the unidirectional extraction ratio (ET), the blood-brain barrier permeability surface area product (PSapp), and PSapp corrected for the unbound fraction (PSuapp) in rats injected with serum from patients with renal failure were significantly reduced to approximately 40-53% of those in controls. No change in BUI, ET, and PSapp was found in rats injected with serum from cirrhotic patients. However, the cirrhotic patients adopted in the present study had relatively mild liver disease (judging from the biochemical blood test), and we cannot refer to the more severe cirrhotic patients only from this study. Moreover, significant correlations were observed between the biochemical parameters (blood urea nitrogen, serum creatinine concentration) representing the degree of renal failure and the transport parameters (ET, PSapp, or PSuapp) of DL-propranolol.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMedDate not supplied

Effects of metallic antioxidants on cadmium-catalyzed peroxidation of arachidonic acid.

In the present study, the reaction mixtures (cadmium chloride with arachidonic acid) were preincubated at 37 degrees C for 24 h prior to the measurement of malondialdehyde (MDA) by high performance liquid chromatography (HPLC). The cadmium-catalyzed reactions were also compared to those in the presence of selenium (Se), zinc (Zn) or germanium (Ge), metallic antioxidants. Our results showed that the toxic effects of cadmium cause lipid peroxidation of arachidonic acid by the catalytic process. The addition of metallic antioxidants to the reaction mixtures, might be useful in protecting against Cd-induced lipid peroxidation.

Antioxidants↗