Search PubMed⌕ Search

Biomedical subjects

T Lin

Publications and source records attributed to T Lin.

At least 109 records · Page 6Linked to original sources
PubMed1997

Retinal dopamine in the recovery from experimental myopia.

PURPOSE: To address further a possible role for retinal dopamine in postnatal eye growth, we studied the response of retinal dopamine in eyes of chicks recovering from myopia. METHODS: Newborn chicks either received a unilateral translucent goggle to induce form deprivation myopia or were reared with unimpaired visual input. The goggle was removed from half of the chicks on day 7. Myopic, recovering and control never-goggled chicks were studied on days 7, 9 and 14. Eyes were enucleated postmortem and measured in axial and equatorial dimensions with calipers. Retinal levels of dopamine and its principal metabolite 3,4-dihydroxyphenylacetic acid (DOPAC) were assayed by high performance liquid chromatography with electrochemical detection. RESULTS: Compared to contralateral and control eyes, retinas of goggled eyes at each time point had reduced levels of dopamine and DOPAC and a lowered calculated DOPAC/dopamine ratio, an index of dopamine metabolism. In eyes recovering from myopia, all biochemical parameters showed prominent increases by 2 days after goggle removal and had reached the level of both contralateral eyes and control eyes by one week after goggle removal. As evidence of a contralateral effect, the retinas of open eyes of chicks wearing a unilateral goggle demonstrated equal dopamine levels but reduced DOPAC compared to eyes of never-goggled chicks. CONCLUSION: An early rise and eventual normalization of retinal dopamine, DOPAC and the DOPAC/dopamine ratio correlate with recovery from myopia. Combined with recent results from lens rearing experiments, these findings suggest that dopaminergic amacrine cells may participate in visually guided eye growth regulation and not just in the myopia response to visual form deprivation. The retinal biochemical alteration in eyes contralateral to a goggle identifies a previously unappreciated binocular interaction in the chick.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1997

Spectrum of mutations in the OCRL1 gene in the Lowe oculocerebrorenal syndrome.

The oculocerebrorenal syndrome of Lowe (OCRL) is a multisystem disorder characterized by congenital cataracts, mental retardation, and renal Fanconi syndrome. The OCRL1 gene, which, when mutated, is responsible for OCRL, encodes a 105-kD Golgi protein with phosphatidylinositol (4,5)bisphosphate (PtdIn[4,5]P2) 5-phosphatase activity. We have examined the OCRL1 gene in 12 independent patients with OCRL and have found 11 different mutations. Six were nonsense mutations, and one a deletion of one or two nucleotides that leads to frameshift and premature termination. In one, a 1.2-kb genomic deletion of exon 14 was identified. In four others, missense mutations or the deletion of a single codon were found to involve amino acid residues known to be highly conserved among proteins with PtdIns(4,5)P2 5-phosphatase activity. All patients had markedly reduced PtdIns(4,5)P2 5-phosphatase activity in their fibroblasts, whereas the ocrl1 protein was detectable by immunoblotting in some patients with either missense mutations or a codon deletion but was not detectable in those with premature termination mutations. These results confirm and extend our previous observation that the OCRL phenotype results from loss of function of the ocrl1 protein and that mutations are generally heterogeneous. Missense mutations that abolish enzyme activity but not expression of the protein will be useful for studying structure-function relationships in PtdIns(4,5)P2 5-phosphatases.

Amino Acid Sequence↗
PubMed1997

Presentation of heterologous peptides on plant viruses: genetics, structure, and function.

Capsid proteins of a number of plant viruses are permissive to genetic modifications in which foreign polypeptides are inserted in exposed loops or at their C termini. Plant viruses with these genetic alterations often grow at wild-type levels, providing gram quantities of modified viruses. Presented polypeptides studied most extensively correspond to antigenic epitopes of animal viruses and in some cases appropriately altered plant viruses generate neutralizing antibodies to the cognate animal virus when the plant virus is used as a vaccine. Structure-based analyses of these animal-plant virus chimeras have led to rational alterations to the presentation in efforts to increase the efficacy of the presented peptide.

Journal Article↗
PubMed1997

[A study on the frequency of sister chromatid exchanges in patients with oral submucous fibrosis in peripheral blood lymphocytes].

The frequency of sister chromatid exchanges (SCEs) in peripheral blood lymphocytes in the patients (n = 27) with oral submucous fibrosis (OSF) with the habit of chewing areca nuts were determined by BrdU-Giemsa staining. The healthy persons (n = 14) with the same habit and the normal controls without the habit (n = 44) were studied at the same time. The results showed that the frequency of SCEs in the first two groups were obviously higher than that in the last one (P < 0.001). The frequency of SCEs in the patients were also higher than that of the healthy persons with the habit (P < 0.001). These suggest that there are some substances in the areca nuts which can induce the mutation and/or malignant transformation of cells. The habit of chewing areca nuts might seriously disturb the stability of chromosome. OSF is a precancer condition. The occurrence of it perhaps has some hereditary background or genetic susceptibility.

Adult↗
PubMed1997

Clonal analysis of the in vivo differentiation potential of keratinocytes.

PURPOSE: This study investigated the in vivo differentiation of conjunctival keratinocytes. METHODS: Keratinocytes from the fornical region of the conjunctival epithelium were isolated and plated at low density (5 x 102 per 100-mm dish) in Dulbecco's minimum essential medium containing 20% fetal bovine serum in the presence of mitomycin C-treated 3T3 feeder cells. At this density, only single, isolated cells were attached after overnight culture. Eight days later, small, well-isolated colonies separated from one another by the feeder cells were detached as a sheet from the dish and were injected subcutaneously into the flanks of BALB/c athymic mice through an 18-gauge needle. Within a day, a small firm nodule appeared at the site of injection. At different time points, the animals were killed, and the nodules were excised for morphologic, histogeometric, and cell kinetic analyses. RESULTS: Each implanted colony derived from a single cell gave rise to a single epithelial cyst lined with a reconstituted stratified epithelium. Goblet-like cells loaded with periodic acid-Schiff-positive cytoplasmic granules began to appear singularly in some of the cysts by day 8 postimplantation and were observed in approximately 85% of the cysts by day 14. CONCLUSIONS: Because the cysts formed were derived from clonal populations of epithelial cells and the majority of cysts had a mixed keratinocyte-goblet cell phenotype, these results suggest strongly the existence of a bipotent precursor cell in conjunctival epithelium that can give rise to both goblet and nongoblet cells. This system can be used to study factors that can influence the commitment of pluripotent epithelial stem cells to divergent pathways of differentiation.

Animals↗
PubMed1997

A hypertension control program in Yu-Chi, Taiwan: preliminary results.

The purpose of this study was to evaluate the feasibility and effectiveness of a community approach to hypertension control in both high risk and general populations in an agricultural district with limited medical and community resources. It was conducted in Yu-Chi district of Nan-Tou county in central Taiwan from 1993 to 1994. The study included blood pressure screening, follow-up, health education, village-based campaigns, and program evaluation after 6 months of intervention. Two villages each were randomly assigned to intervention and control groups. Intervention comprised visits by trained volunteers to measure blood pressure and body weight, and education related to hypertension. All residents 40 years of age and older were enrolled. A total of 471 residents from the intervention villages and 426 residents from the control villages completed the study. Overall, for the intervention and control groups, the knowledge and behavior related to hypertension improved significantly 6 months after the baseline survey. The improvement was greater in the subgroup of hypertensives in the intervention group than in the controls. The educational intervention also significantly improved the status of awareness, treatment, and the control of hypertension, and reduced blood pressure in the hypertensive subjects. We conclude that a hypertension control program that relies solely on limited community resources is feasible and effective.

Adult↗
PubMed1996

Reversion of monochromosome-mediated suppression of tumorigenicity in malignant melanoma by retroviral transduction.

We have developed a general strategy to reverse monochromosome suppression of the malignant phenotypes by retroviral transduction. Our approach involved the introduction of a retroviral expression vector-carried cDNA library into a chromosome 6-suppressed melanoma subline UACC-903(+6) [J. M. Trent et al., Science (Washington DC), 247: 568-571, 1990]. The cDNA library was constructed from polyadenylated RNA isolated from the suppressed UACC-903(+6) cells, packaged into high-titer amphotropic retrovirus particles, and transduced into UACC-903(+6) cells. Revertant his(R) transductants were selected by isolating colony-forming cells in soft agar. A total of 121 large (> 150 microm) colonies was picked from soft agar culture with 18 of 121 (15%) established as permanent sublines. The revertant sublines demonstrated 7-58% cloning efficiency upon plating in agar, in contrast to <0.05% for the UACC-903(+6) subline. All 18 revertant sublines, termed SRS1-SRS18 (for "selection of revertants for suppression"), displayed a reduced population-doubling time, with 9 of 18 showing focus formation in monolayer similar to the parental (nonsuppressed) cell line. Preliminary evidence for reversion of the suppressed phenotype by injection of cells into athymic nude mice has been completed for one revertant subline. Southern analysis has demonstrated integration of the retroviral vector sequence in all 18 sublines. This approach should facilitate the identification of genes involved in the tumorigenic phenotype of malignant melanoma, and is readily adaptable to other model systems.

Base Sequence↗
PubMed1996

Thymus ontogeny and the development of TCR alpha beta intestinal intraepithelial lymphocytes.

Murine T cell receptor (TCR) alpha beta intestinal intraepithelial lymphocytes (IEL), which express the CD8 molecule as a homodimer (CD8 alpha alpha), can be divided into two subsets: those which are CD4+ (CD4+CD8+alpha alpha) and those which are CD4- (CD4-CD8+alpha alpha). Here, we demonstrate that most TCR alpha beta CD4+CD8+alpha alpha IEL and TCR alpha beta CD4-CD8+alpha alpha IEL subsets appear to be of thymus origin, as neonatal thymectomy of BALB/c mice on Day 3 nearly eliminated both subsets. To further support this hypothesis, we demonstrate by grafting the thymus of CBF1 (BALB/c x C57BL/6) mice into nude mice that the thymus is capable of generating both TCR alpha beta CD4-CD8+alpha alpha IEL and TCR alpha beta CD4+CD8+alpha alpha IEL. However, which of the two TCR alpha beta IEL subsets is generated depends largely on the age of the thymus. The thymus from fetal up to 2 weeks of age generates predominantly TCR alpha beta CD4-CD8+alpha alpha IEL, but very scant amounts CD4+CD8+alpha alpha IEL. In contrast, the thymus after 2 weeks of age generates very little TCR alpha beta CD4-CD8+alpha alpha IEL, but generates an abundant amount of TCR alpha beta CD4+CD8+alpha alpha IEL. These results are consistent with the observation in euthymic mice that TCR alpha beta CD4-CD8+alpha alpha IEL precede the appearance of TCR alpha beta CD4+CD8+alpha alpha IEL by several weeks, thus further suggesting that the thymus is the major source of both TCR alpha beta IEL subsets.

Aging↗
PubMed1996

Altered CD45 expression in malignant B-1 cells.

CD45 is an important surface glycoprotein which has an intrinsic tyrosine phosphatase activity and has been implicated in cell proliferation, signaling, and differentiation and is associated with the B cell receptor during signaling. In this manuscript, the role of CD45 expression in the development of B-1 malignancies in NZB mice, which serve as a model for human diseases such as chronic lymphocytic leukemia, was investigated. B-1 cells spontaneously hyperproliferate and form a clonal hyperdiploid malignant population in aging NZB mice. Phenotypic analysis indicates that the NZB malignant B-1 cells are bright for IgM, but have reduced levels of CD45 relative to normal, nonmalignant B cells (both B-1 and B-2) and are characterized by dull or negative expression of the CD45 isoform B220/6B2 normally found on all B cells. Malignant B-1 cells demonstrated decreased RNA levels of CD45 relative to IgM expression, while nonmalignant B-2 cells showed similar levels of RNA expression for both CD45 and IgM. As CD45 exists in several isoforms and B cells express the highest molecular weight isoform (B220), malignant B-1 cells were further analyzed with respect to their isoform usage. Although, at the RNA level malignant B-1 cells showed the presence of the of the B220 form of CD45, western blot analysis of B220 protein suggested a posttranslational glycosylation defect in the CD45/B220 expression recognized by the mAb 6B2. F1 recipients of premalignant NZB B-1 cells which had been sorted for IgMhi, B220/6B2negative cells developed hyperdiploid malignant donor B-1 clones earlier than did recipients of NZB B-1 cells which were bright for B220/6B2. However, all the malignant B-1 clones of NZB origin which developed in recipients of both transfer populations were B220/6B2 negative. This indicated that abnormal expression of CD45 may be prerequisite for long-term growth and malignant transformation. Thus alterations in CD45 may result in abnormal functioning of the malignant B-1 cells which may further affect the proliferation of, or signaling within, these cells.

Animals↗
PubMed1996

Inadequate history as a barrier to immunization.

OBJECTIVES: To evaluate how lack of immunization history contributes to missed opportunities for immunization and to document the effort required to obtain immunization history. DESIGN: Cross-sectional. SETTING: Urban, inner-city primary care pediatric clinic serving a low-income, multiethnic population. PATIENTS: Ninety-five new patients seen for either well-child care (53 patients) or acute illnesses (42 patients) during a 4-month period in 1993. Fifty-nine patients were aged 3 to 59 months and 36 were aged 5 to 15 years. MEASUREMENTS: Efforts to obtain immunization history were documented by means of a standardized data collection form. RESULTS: Immunization history was obtained for only 26 (27%) of 95 patients during the initial visit. Caregivers of 74 (78%) of 95 patients did not bring immunization records to the initial visit; they were no more likely to bring records for well-child care than for acute care or for younger vs older children. Parents brought immunization records more often than did nonparents. A total of 145 telephone calls were made and 30 letters were sent in an attempt to obtain immunization histories. Immunization records were never found for 10 new patients (11%). Thirty-two patients (34%) were found to be lacking immunizations. Of these, only three patients had contraindications to immunization at the initial visit. Therefore, in one third of our new patients, opportunities to immunize were missed solely because their immunization records were unavailable at the initial visit. In another one third of cases, caregivers had incorrectly believed their child's immunizations to be up to date. CONCLUSIONS: Opportunities to immunize children were often missed because of a lack of immunization history. Our experience supports the need for improved documentation of immunization histories.

Adolescent↗
PubMed1996

Pharmacokinetics and pharmacodynamics of multiple-dose terbinafine.

Data from clinical trials of terbinafine for the treatment of onychomycosis were analyzed with the following two objectives: 1) to identify demographic predictors of the duration and extent of systemic drug exposure; and 2) to explore whether increased systemic exposure or demographic predictors of increased exposure were associated with altered safety or efficacy. Demographic predictors of exposure were identified by a model-free, nonparametric approach applied to the sparse pharmacokinetic data from the onychomycosis studies. Those covariates were then incorporated into a multicompartmental nonlinear mixed effects model. Post hoc parameter estimates from the nonlinear mixed effects model provided individual measures of exposure. Safety scores were derived for adverse events that were frequently attributed to drug exposure and for liver function tests. Terbinafine was found to have an average terminal half-life (t1/2) of approximately 3 weeks. That terminal elimination phase contributed so little to the total exposure, however, that average concentrations accumulated only approximately two-fold at steady state with once daily dosing. Age and concomitant hypertension were predictors of higher plasma concentrations of terbinafine; smokers had lower levels than nonsmokers. Although some statistically significant associations between adverse events and systemic exposure were found, in all cases the actual frequency of the adverse events and systemic exposure were found, in all cases the actual frequency of the adverse events was low, and there were no trends in severity with respect to exposure. Above-normal levels of gamma-glutamyl transferase were associated with exposure, but there was no trend in severity with respect to exposure. No other liver function test abnormalities were associated with exposure, nor were there any significant associations between adverse events or liver function abnormalities and demographic subgroups that differed with respect to exposure. Among patients taking the active drug there were no significant associations between exposure levels and efficacy, nor were there differences in efficacy between demographic subgroups that differed with respect to exposure.

Adult↗
PubMed1996

Care of the adult with phenylketonuria.

Forty-three adults with classical phenylketonuria were identified by neonatal screening and treated with a phenylalanine (Phe) restricted diet. Nineteen have remained on dietary treatment with varying levels of blood Phe control and 24 have discontinued the diet at an average age of 7.8 years. Follow up at an average age of 22 years revealed that the cohort remaining on dietary treatment have achieved substantially better social and academic achievement than the 24 who discontinued dietary treatment. Another group of 19 adults who were not diagnosed until an average age of 2.5 years have also been evaluated after an average of 22 years on a Phe restricted diet. This report is based upon Wechsler Adult Intelligence Revised Test scores, attendance at college, employment and marital status.

Adolescent↗
PubMed1996

Clinical and hematologic effects of hydroxyurea in children with sickle cell anemia.

PURPOSE: This open-label pilot study was designed (1) to determine the effect of hydroxyurea on the hemoglobin level in children with sickle cell anemia, (2) to evaluate the toxicity of hydroxyurea, and (3) to assess any impact of hydroxyurea on the frequency of vaso-occlusive crises (VOCs). PATIENTS AND METHODS: Ten children (group 1) with three or more VOCs of the extremities or two or more VOCs of the lungs (acute chest syndrome) in the preceding 12 months, and five children (group 2) with hemoglobin levels less than 70 gm/L were treated with hydroxyurea in doses of 20 to 35 mg/kg per day. The frequency of VOCs before hydroxyurea therapy was compared with the frequency during therapy, and the peak hemoglobin levels during hydroxyurea therapy were compared with the pretreatment values. RESULTS: One patient in group 1 was removed from the study within 1 month because of nausea. Seven of the remaining nine patients in group 1 had a decrease in the frequency of VOCs. The number of VOCs per patient-year for all 14 patients decreased from 2.5 before hydroxyurea therapy to 0.87 during hydroxyurea therapy, a decrease of 65% (p < 0.00001). Two of five patients in group 2 had an increase in hemoglobin of 27 gm/L and 34 gm/L over the baseline. The median rise in hemoglobin was 19 gm/L (range, 7 to 37) for all 14 patients. Nine patients are still receiving hydroxyurea for a median period of 23 months (range, 18 to 59). CONCLUSIONS: Hydroxyurea decreases the severity of anemia in some patients, and it may decrease the frequency of VOC. Its short-term hematologic toxicity is minimal.

Adolescent↗
PubMed1996

Structure-based design of peptide presentation on a viral surface: the crystal structure of a plant/animal virus chimera at 2.8 A resolution.

BACKGROUND: We employed a genetically engineered icosahedral plant virus, cowpea mosaic virus (CPMV), as an expression and presentation system to display a 14 amino acid linear antigenic epitope found in a capsid protein of human rhinovirus 14 (HRV14). RESULT: Gram quantities of the CPMV/HRV 14 chimera were made in plants and purified particles were crystallized in a form isomorphous with wild-type CPMV. The 2.8 A resolution structure of the chimera shows that the inserted loop is well ordered and that if the loop were intact, a phenylalanine residue of CPMV would be placed in a hydrophilic environment. The resultant strain may make the loop an attractive substrate for endogenous plant proteases, as roughly 80% of the inserted polypeptides are cleaved, allowing the phenylalanine to be partially buried. Altering the phenylalanine to an arginine could relieve the stress, reducing the propensity for cleavage and increasing the likelihood that the peptide will assume a structure closely similar to its structure in HRV14. CONCLUSIONS: Successful crystallization of other CPMV chimeras in forms isomorphous with the native virus suggests that this is a viable system for structure-based design of peptide presentation.

Amino Acid Sequence↗
PubMed1996

The development of cowpea mosaic virus as a potential source of novel vaccines.

Epitopes from human rhinovirus 14 (HRV-14) and human immunodeficiency virus type (HIV-1) have been expressed on the surface of particles of the plant virus, cowpea mosaic virus (CPMV). The chimaeras retain their ability to grow in plants and large quantities of virions can be easily purified. Immunological studies have shown that purified particles have the antigenic properties of the insert, and, in the case of the HIV-1 chimaera, can elicit the production of neutralising antibodies in mice. The chimaera containing the epitope from HRV-14 has been crystallised and the crystals shown to diffract to atomic resolution.

AIDS Vaccines↗
PubMed1996

The ciliary ganglion and vitreous cavity shape.

PURPOSE: To learn the influence of the ciliary ganglion on the postnatal growth of eyes with unimpaired visual input and of eyes beneath an image diffusing goggle. METHODS: Newborn chicks received unilateral ciliary ganglionectomy or unilateral sham operation and were reared either with or without a goggle ipsilateral to the surgical procedure. Ocular refractions and ultrasound measurements were made on anesthetized chicks; eyes enucleated postmortem were measured in axial and equatorial dimensions with calipers and studied histologically. RESULTS: Excessive growth of open eyes in the equatorial dimensions followed ciliary ganglionectomy and became more pronounced as the chicks grew older. There was only a modest increase in axial growth. Ganglionectomy also induced relative hyperopia; lens thinning contributed to this effect and likely was a direct result of disrupted parasympathetic input to the ciliary muscle. Ganglionectomy also slightly increased the thickness of the choroid in the posterior pole but not in more peripheral locations. CONCLUSION: We conclude that the ciliary ganglion exerts an inhibitory influence on the postnatal growth of open eyes; the main effect is in the equatorial dimension of the vitreous cavity, with a smaller effect on axial length. Ciliary ganglionectomy exerted minimal influence on the development of experimental myopia, known to be induced by the goggle regimen. The amount of equatorial expansion in goggle-induced myopia was greater than after ganglionectomy alone, indicating that other factors besides the ciliary ganglion can influence the equatorial dimension of the vitreous cavity.

Animals↗
PubMed1996

Validation of laser Doppler interferometric measurements in vivo of axial eye length and thickness of fundus layers in chicks.

Purpose. Laser Doppler interferometry (LDI) permits the measurement of intraocular distances to a precision of better than 20 microm. The signal complex from the posterior segment of the eye consists of four peaks in the chick, an animal frequently used in ocular development studies. The present study sought to identify anatomical landmarks corresponding to these LDI peaks. Methods. Distances obtained with LDI at the posterior pole were compared to axial length components measured with three independent methods: vernier calipers, tissue sections and high frequency A-scan ultrasound. Results. LDI reflections appear to originate from the retinal inner limiting membrane, Bruch's membrane and the inner and outer scleral surfaces. Conclusions. The non-invasive and highly precise nature of LDI measurements enables repetitive and accurate assessment of intraocular distances. Such measurements should prove particularly useful for the assessment of short-term cyclic variations in intraocular distances as well as post-natal eye growth.

Animals↗