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Biomedical subjects

K P Cheng

Publications and source records attributed to K P Cheng.

29 records · Page 2Linked to original sources

Efficacy of glycoprotein inhibitors alone and in combination with trifluridine in the treatment of murine herpetic keratitis.

The present study examined the anti-herpetic effect of the glycoprotein inhibitors, hydroxynorvaline and 2-deoxyglucose, alone and in combination with trifluridine on murine ocular herpes. Following ocular inoculation with a large dose of HSV-1 RE strain (10(6) pfu), ICR mice were treated during the acute infection with different therapeutic regimens, and their efficacy was evaluated by ocular virus titers, clinical grading of blepharo-conjunctivitis and histological evaluation of stromal keratitis and iridocyclitis. The results following a large dose HSV-1 inoculum demonstrated that trifluridine was the best single therapeutic agent. Hydroxynorvaline and 2-deoxyglucose had no effect at all. Combination therapy of the glycoprotein inhibitors with trifluridine was no better than trifluridine alone. The mouse HSV-1 keratitis model proved to be an effective, economical alternative to the rabbit model for the evaluation of new antiviral agents.

Animals↗

The development of an improved murine iontophoresis reactivation model for the study of HSV-1 latency.

The present study reviews the development of an effective murine iontophoresis reactivation model for the study of HSV-1 latency. In a series of experiments, Balb C mice latently infected with HSV-1 McKrae strain were iontophoresed with epinephrine X 3 days (EPI X 3/ION) or 6-hydroxydopamine X 1 day followed by topical epinephrine (6-HD ION/EPI). Reactivation and recovery of latent HSV-1 was determined by daily ocular swabs, titration, and neutralization. Additional studies determined the effect of topical ocular steroids on viral recovery rate. The results demonstrated no recovery of McKrae strain in Balb C (0%) with EPI X 3/ION, and no enhancement with topical steroids. 6-HD ION/EPI demonstrated a low recovery rate in mice (8%). However, the recovery rate was significantly increased to 50% by the addition of topical steroids to form the 6-HD ION/EPI/STEROID model, a useful experimental tool. The substitution of a clinical isolate, W strain, for McKrae strain further improved the model. The results demonstrated that, following the acute infection in mice, W strain was associated with a significantly higher (P = .001) survival rate than McKrae strain (81% vs. 52%). There was no statistically significant difference between the two strains, W vs McKrae, in Balb C mice comparing keratitis, establishment of latency (by co-cultivation), spontaneous shedding rate, or induced ocular shedding following iontophoresis. The development of an effective murine iontophoresis model offers an economical method which is uniquely suited for immunological and genetic studies of HSV-1 latency.

Administration, Topical↗

Enkephalin degradation stimulated by captopril.

Changes in the rates of degradation of Met- and Leu-enkephalin by brain aminopeptidase were measured by UV absorption after high-pressure liquid chromatography. The cleavage of enkephalin paralleled the generation of tyrosine. Captopril (SQ 14,225) stimulated enzyme activity, to a greater extent with Met- than with Leu-enkephalin. Pro-His-Pro-NH2, histidine, and histamine stimulated enkephalin aminopeptidase approximately twice as much as captopril. The sulfhydryl group of captopril was not the only factor in its effect. The addition of captopril did not change the pH optimum, and it stimulated enkephalin degradation between 25 and 50 degrees C.

Aminopeptidases↗

Degradation of melanotropin inhibiting factor by brain.

Degradation of melanotropin inhibiting factor (MIF) was measured by fluorometry, using pareptide as an internal standard, following the separation of the dansyl derivatives of MIF and its metabolites by HPLc. MIF was not split by carboxypeptidases A and B, prolidase, or pyroglutamate aminopeptidase. It was hydrolyzed by leucine aminopeptidase, aminopeptidase M, and carboxypeptidase Y. Rat brain hydrolyzed 159 nmol of MIF per mg of protein per h; the activity was linear with enzyme concentration. Hydrolysis start from the N-terminal end, as shown by the appearance of proline as the first metabolite of the MIF degradation, followed by leucine, glycinamide, leucylglycine, and glycine. Activity in the rat brain regions was in the order striatum, medulla oblongata > cortex, hippocampus, midbrain > hypothalamus, cerebellum, and pituitary. The enzyme was mostly in the supernatant, with significant amounts in the myelin and synaptosomal fractions. MIF aminopeptidase could be separated from carboxypeptidase by centrifugation at 30,000 x g for 20 min and precipitation with 45--75% (NH4)2SO4. It showed pH optima in the alkaline range (8.25 and 8.75) and was inhibited by EDTA, EGTA, SQ 14,225, puromycin, bacitracin, and bestatin.

Aminopeptidases↗

Clinical and upper gastroendoscopic features of patients with dengue virus infection.

Clinical observation was made on 238 dengue fever cases during an epidemic in Taiwan from September to November 1988. Dengue virus infection type 1 was responsible for all cases. The majority of patients had acute onset of fever with abdominal pain, diarrhoea, and vomiting. Gastrointestinal haemorrhage with manifestation of haematemesis and/or melena was observed in 28 (11.8%) of our patients. The clinical gastrointestinal features in patients with a peptic ulcer history were not different from those in patients without it. There was no significant difference in incidence of gastrointestinal manifestations between premedication and non-premedication patients. Sixty-six non-premedication patients in our series were examined by gastroduodenoscopy. Haemorrhagic gastritis was the most common finding in 27 (40.9%) patients. The incidence of gastric and/or duodenal ulcerations was higher in patients with a peptic ulcer history compared with those without it (P less than 0.01). However, the incidence of upper gastrointestinal bleeding was similar between these two groups (19.2% vs 9.8%). Thrombocytopenia in patients with gastrointestinal haemorrhage was more prominent than in those without it (P less than 0.005). This implied that thrombocytopenia might be one of the predisposing factors for gastrointestinal haemorrhage.

Adult↗

Management of posterior lenticonus.

Posterior lenticonus is associated with progressive lens opacification. We report a series of 40 consecutive patients (41 eyes) with posterior lenticonus who were treated by three pediatric ophthalmologists between 1974 and 1988. Prior to cataract surgery, appropriate patients were treated with atropine dilatation, spectacle correction including bifocals for refractive errors, and amblyopia occlusion therapy. Indications for surgery were a measured decrease in visual acuity, the loss of a central fixation reflex, or the onset of strabismus. The age at which cataract surgery was performed ranged from 2 months to 12 years (mean 4 years, 6 months). Nineteen eyes (49%) achieved postoperative acuities in the 20/20 to 20/40 range, 7(18%) eyes achieved 20/50 to 20/100, 4 (10%) eyes achieved 20/200, and 4 (10%) eyes achieved less than 20/200. Two (5%) young patients had central, steady, and maintained visual fixation reflexes and 3 (8%) additional patients had central, steady, but not maintained reflexes. After cataract surgery and aphakic optical correction, amblyopia was present in 84% of patients and strabismus was present in 51% of patients. The patients in this study had sufficient optical distortion to produce amblyopia. Cataract removal and optical correction alone did not correct the vision; occlusion therapy for amblyopia was required. Earlier surgery may be indicated to prevent visual deprivation amblyopia in patients with posterior lenticonus.

Amblyopia↗

Infantile exotropia.

BACKGROUND: Exotropia is uncommon in healthy children between 6 months and 1 year old. METHODS: The charts of patients treated in our practice between January 1980 and August 1994 were reviewed for a diagnosis of infantile exotropia. All of them had an exodeviation during the first year of life. Children with neurologic defects, prematurity, trauma, craniofacial syndromes, or orbital abnormalities or ocular defects that would reduce vision were eliminated. RESULTS: Sixty-six healthy patients with normal eyes had an exodeviation of 15 prism diopters (delta) or more that persisted through the first year of life. Fifty-four were eliminated because the diagnosis had not been confirmed by a pediatric ophthalmologist before they were 1 year old or they had not been followed for more than 4 years. The 12 remaining patients were followed for at least 4 years (mean, 7.9 years). The mean age at the first examination was 7.8 months (range, 4 to 12 months). On early evaluation, exotropia was intermittent in four and constant in eight. Three had amblyopia. Ten required surgical correction. Exotropia was corrected with one operation in six patients; four required additional procedures, mostly to correct oblique muscle overaction and dissociated vertical deviation (DVD). At the most recent visit, all 12 patients had equal visual acuity in both eyes and satisfactory ocular alignment. Five had fusion at distance and near, but only two had stereo acuity of 100 seconds of arc or better. CONCLUSION: Infantile exotropia is rare. But, like patients with infantile esotropia, those with exotropia can be expected to have good visual acuity but unstable ocular alignment. Also, as with early-onset esotropia, although surgical intervention is usually required, high levels of binocular function develop in some patients with exotropia. Oblique muscle overaction and DVD are common, often becoming manifest by the first year of age. Unlike infantile esotropia, nystagmus is rare.

Depth Perception↗

Congenital aphakia: a clinicopathologic report of three cases.

BACKGROUND: Congenital aphakia is a rare condition that has been classified as primary when no lens induction of the surface ectoderm occurs and secondary when lens development takes place but later is resorbed or expelled in utero. METHODS: The authors report the clinical and pathologic findings in three infants with congenital aphakia whose eyes were enucleated either at surgery at 11 months or at autopsy after 1 and 3 days of life. RESULTS: Two cases classified as primary congenital aphakia had severe microphthalmos, anterior segment aplasia, or anomalous development and posterior choroidal and optic disc colobomas. One was in a case believed to be Waardenburg's recessive anophthalmia syndrome and the other had 18 trisomy. A case of secondary congenital aphakia had findings of Peter's syndrome and features suggesting rubella, which had been observed in some previous reports. CONCLUSIONS: Primary congenital aphakia can result from a variety of teratogenic events in the first 4 weeks of embryogenesis and results in microphthalmos and severe anterior segment aplasia/dysplasia. Secondary congenital aphakia is associated with less severe ocular anomalies. The possible role of deletion or mutation involving the PAX6 gene in anterior segment anomalies and induction of lens development is discussed. In addition to chromosomal influences, in utero viral infection, particularly rubella, may play a role in some cases.

Abnormalities, Multiple↗