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Biomedical subjects

C H Yen

Publications and source records attributed to C H Yen.

11 recordsLinked to original sources

[A frontal cephalometric analysis].

A comprehensive frontal cephalometric analysis was developed and its normal values for Chinese adults were established in this study. This analysis includes two parts: width proportional analysis and symmetry analysis. Most linear width values of males were significantly greater than those of females as expected. However, there were no significant sex differentials in the most width ratios. Among these, the ratio Go/Z reached ca. 75%, Mx/Zy ca. 50%, L6/Go ca. 50% and the Mx/Go ca. 66.6% (2/3). Width problems and possible expansion at canine and molar areas could be evaluated through proportional analysis. To determine the locations as well as extents of dentofacial asymmetry is of great clinical value especially in orthodontic treatment. In symmetry analysis, linear differences between both side structures in vertical and horizontal directions could be calculated.

Adult

Identification of a new binding protein for crotoxin and other neurotoxic phospholipase A2s on brain synaptic membranes.

Crotoxin and other neurotoxic phospholipase A2s exert neurotoxicity by acting primarily at the presynaptic level. Strong binding of crotoxin and several others to synaptic membranes has been demonstrated previously. In this study we used simple chemical cross-linking techniques to identify the neuronal membrane molecules involved in the binding of these toxins. After 125I-crotoxin had bound to synaptosomes from guinea pig brain, treatment with disuccinimidyl suberate, disuccinimidyl dithiobis(propionate) or ethylene glycol bis(succinimidyl succinate) resulted in the formation of a predominant radioactive conjugate of approximately 60 kDa, which was different from the conjugate formed by photoaffinity labeling technique in a previous report. The membrane component in the conjugate was shown to be a single-chain protein of approximately 45 kDa. In subfractions of synaptosomes, this binding protein was mostly found in the synaptic membrane fraction and was not present in the mitochondrial fraction. Plasma membranes from several nonneural tissues also did not contain this binding protein. Unmodified crotoxin inhibited the formation of this adduct with an IC50 of around 1 x 10(-8) M. Mojave toxin and some other phospholipase A2s were also highly inhibitory to this conjugation, and notexin and others were less effective, while beta-bungarotoxin and pancreatic PLA2 were totally ineffective. We concluded that a new protein of 45 kDa specifically present in neuronal membranes is another major molecule responsible for the binding of crotoxin and other phospholipase A2s.

Animals

DNA variants with telomere probe enable genetic mapping of ends of mouse chromosomes.

Dde I-digested DNA fragments from 11 inbred mouse strains were separated by electrophoresis, blotted and probed with a labeled oligomer, TELO, containing five repeats of the consensus mammalian telomere sequence, TTAGGG. Each strain produced a unique set of hybridizing fragments. Segregation analysis of TELO-hybridizing fragments from the BXD RI strains indicated that each fragment segregated as expected for a single gene. One fragment from strain DBA/2J was genetically linked to locus Xmv-9, previously mapped near the distal end of the map of chromosome (Chr) 4 and three fragments to Cck, near the distal end of Chr 9, suggesting that these fragments are telomeric and represent the ends of the chromosome maps. Confirmation of these map positions was obtained from a backcross. Fragments associated with the short arm of the Y Chr were found in DNA from strains C57BL/6J and DBA/2J. TELO-hybridizing fragments from DBA/2J were digested by the exonuclease Bal 31, under conditions in which fragments hybridizing to a cDNA probe for the metallothionein locus, located at the middle of mouse Chr 8, remained intact. Thus both biochemical and genetic tests indicate that several TELO-hybridizing fragments from Dde I-digested DNA are at the ends of chromosomes and probably derive from mouse telomeres. Using this approach should allow the mapping of genes relative to the ends of other mouse chromosomes.

Animals

[Computerized cephalometric analysis in clinical use].

In making a computerized cephalometric analysis, first the film should be traced, and the landmarks pricked and manually digitalized into an X-Y coordinate system. The computer's analysis program registers for the landmarks, automatically calculates the angles and line distances, and then compares these values to the norms. The computer can also print out the measurements and draw a computer-produced graph on request. Such a procedure is convenient and yields more accurate results. The most common mistake, picking in the wrong sequence, can be controlled by carefully inspecting the computer-produced graph.

Cephalometry

[An electron microscopic study of migrating cells in the nasal epithelial compartment of human allergic rhinitis].

Since intraepithelial migrating cells are the first to come into contact with various foreign particles inhaled and deposited on the nasal surface, it is important to study the distribution and function of these cells in the epithelial layer of nasal mucosa. We examined nasal scrapings by means of electron microscopy and electron microscope immunocytochemistry and found that lymphocytes were the major population in the epithelial layer, followed by eosinophils, basophilic cells, globule leukocytes and neutrophils in the order of predominance in patients with allergic rhinitis. However, no significant difference was noted in lymphocyte population between the allergy group and the chronic infectious rhinitis group, while significant increase was found in the normal group than in other two groups. Meanwhile, significant difference of eosinophils and basophilic cells were found between allergic group and non-allergic group. Globule leucocytes, characterized by their huge and irregular size and granules, were observed in the allergy group and the implication of their existence was discussed. In immunoelectron microscopic study, CD8 positive cells were more numerous than CD4 positive cells. However there was no relation between the surface marker and ultrafine structure.

Cell Compartmentation

[The individualized ANB angle of Chinese adults].

The ANB angle is commonly utilized to determine sagittal jaw relationships in cephalometric analysis. The ANB angle may be affected by other factors; therefore, its correlation to another measurement should be further recognized. This will eliminate the possibility of a biased interpretation. The individual variation of the ANB angle was investigated in 80 lateral radiographic cephalograms. The sample consisted of 40 Chinese male and 40 Chinese female adults. All of the sample had neutral molar relationships (Class I), and balanced profiles; none had previously undergone orthodontic treatment. ANB, SNA, SN-MP angles and SN were calculated for each gender. Multiple regression analyses and regression equation were performed and established. The results indicate that the variation of the ANB angle can be explained by the variations of the SNA and SN-MP angles. The males had less mandibular divergency than females (p less than 0.05); resulting in a different effective pattern. The derived equations are: ANBind = 0.42 x (SNA) + 0.31 x (SN-MP) - 41.1 for males; ANBind = 0.31 x (SNA) + 0.20 x (SN-MP) - 28.9 for females. The explanation power also showed gender difference: males 56.2%, females 24.2%. The ANB angle for different facial types are presented through equation-produced lists of individualized norms. These norms aid the interpretation of the individual variations.

Adult

Taipoxin-binding protein on synaptic membranes: identification by affinity labeling.

Affinity labeling techniques were used to identify the neuronal membrane molecules involved in the binding of taipoxin, a neurotoxic protein with phospholipase A2 activity. After [125I]taipoxin had bound to synaptosomes from guinea pig brain, treatment with disuccinimidyl suberate resulted in the formation of a predominant radioactive conjugate of 60,000 Da. Notexin and some other PLA2s are weakly inhibitory to this conjugation, while beta-bungarotoxin and some others are not inhibitory. The 60K conjugate was not detected when plasma membranes from several nonneuronal tissues were used. We concluded that a 45,000 Da protein specifically present in neuronal membranes is (a subunit of) the major molecule responsible for taipoxin binding.

Affinity Labels

Substituted 2-[(2-benzimidazolylsulfinyl)methyl]anilines as potential inhibitors of H+/K+ ATPase.

A series of substituted 2-[(2-benzimidazolylsulfinyl)methyl]anilines were synthesized as potential inhibitors of the acid secretory enzyme H+/K+ ATPase. Substitutions on the aniline nitrogen atom resulted in potent enzyme inhibition in vitro but weak activity in gastric fistula dogs. Electron-donating substituents on the aniline ring enhanced in vitro and in vivo potency relative to the unsubstituted analogue. The potency showed a correlation to the calculated pKa of the aniline nitrogen atom. Substitutions on the aniline and benzimidazole rings did not further enhance potency. Di- and trisubstituted aniline derivatives were potent inhibitors of the enzyme system. The preferred combination of substituents were a methoxy group on the benzimidazole ring and a single alkyl group on the aniline ring. One such compound, 76, was an effective inhibitor of acid secretion in the dog and was selected for further pharmacological study.

Adenosine Triphosphatases

The pharmacology of SC-27166: a novel antidiarrheal agent.

SC-27166 is the result of continuing efforts to discover selective and orally active antidiarrheal agents. SC-27166, which is chemically unrelated to opiates or neuroleptics, possesses potent constipating and antidiarrheal activity in several animal models. Tolerance to the constipating actions of SC-27166 did not develop in mice. On the other hand, gut tolerance rapidly developed to morphine sulfate and loperamide. The basic mechanism of the antidiarrheal action of SC-27166 is a consequence of increased intestinal circular muscle contractile activity. Supportive pharmacological studies indicated that SC-27166 has equivocal analgesia in mice which is manifested at near toxic dose levels. SC-27166 was also evaluated for potential dependence liability in morphine abstinence-induced jumping in mice. The abstinence-induced jumping was suppressed to a far lesser extent by SC-27166 than by either loperamide or diphenoxylate at equal doses. SC-27166 was also devoid of anticbholinergic activity. When compared with the reference standards morphine and diphenoxylate, these pharmacological studies indicated that SC-27166 has a high degree of separation of undesirable central nervous system actions from its antidiarrheal properties and may have important therapeutic potential.

Analgesics

3,3-Diphenyl-3-(2-alkyl-1,3,4-oxadiazol-5-yl)propylcycloalkylamines, a novel series of antidiarrheal agents.

A series of 4-amino-2,2-diarylbutyronitriles (3) prepared for testing as inhibitors of gastrointestinal propulsive activity did not show any enhancement over such existing agents as diphenoxylate and loperamide. However, conversion of the nitrile group to a 2-methyl-1,3,4-oxadiazol-5-yl function led to compounds 5g and 5j, statistically equipotent to diphenoxylate and loperamide in the mouse and showing a very low order of analgesic activity. Structural modifications determined that the best separation of antipropulsive and analgesic effects was obtained when the amino group was bicyclic and the oxadiazole ring had a 2-methyl substituent. The most potent compounds were and analogues of diphenoxylate and loperamide where the oxadiazole ring was present, but these compounds had marked analgesic activity.

Amines