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T Lin

Publications and source records attributed to T Lin.

At least 127 records · Page 7Linked to original sources
PubMed1995

Development of TCR-gamma delta CD4-CD8+ alpha alpha but not TCR-alpha beta CD4-CD8+ alpha alpha i-IEL is resistant to cyclosporin A.

Present evidence suggests that cyclosporin A (CSA) inhibits the development of both alpha beta and gamma delta T cells in the thymus. However, whether CSA can inhibit the development of murine intestinal intraepithelial lymphocytes (i-IEL) is unknown as most i-IEL are clearly derived from a different lineage than the conventional thymus-derived T cells found in the periphery. Using the adult thymectomized, lethally irradiated bone-marrow reconstituted chimera (ATXBM mice) as a model for the development of extrathymically derived i-IEL and the fetal thymus-grafted (FTG) nude mice as a model for the development of thymically derived i-IEL, we demonstrate that CSA nearly completely inhibited the development of extrathymically, and possibly thymically, derived TCR-alpha beta i-IEL. Most of the TCR-alpha beta i-IEL whose development was inhibited by CSA belonged to the CD4-CD8+ alpha alpha subset. In contrast, the development of extrathymically and thymically derived TCR-gamma delta i-IEL was completely resistant to CSA. The phenotype of CSA-resistant TCR-gamma delta i-IEL in these models was not different from those in control mice, and the TCR-gamma delta i-IEL in CSA-treated mice appear to be mature and activated as most were large, granular, and CD69+. Lastly, we demonstrate that CSA does not affect the extrathymic positive selection of V delta 4 i-IEL in C3H hosts. These results suggest that despite their similarity, the intracellular activation cascade involved after TCR stimulation between TCR-alpha beta CD4-CD8+ alpha alpha and TCR-gamma delta CD4-CD8+ alpha alpha i-IEL are markedly different.

Animals↗
PubMed1995

A role for CNS alpha-2 adrenergic receptors in opiate-induced muscle rigidity in the rat.

A number of potential neurochemical mediators of opiate-induced muscle rigidity have been proposed based on the results of systemic drug studies and on knowledge of the brain sites implicated in opiate rigidity. The effects of i.c.v. pretreatment with selected opioidergic, alpha adrenergic and serotonergic drugs on muscle rigidity induced with systemic injection of the potent opiate agonist alfentanil (ALF) were investigated in spontaneously ventilating rats. The opiate antagonist methylnaloxonium (MN; 0.2-14 nmol), alpha-2 adrenergic agonists dexmedetomidine (DEX; 0.4-42 nmol) or 2-(2,6-diethylphenylamino)-2-imidazoline hydrochloride (ST91; 4-400 nmol), alpha-1 adrenergic antagonist prazosin (PRZ; 7-70 nmol) or serotonergic antagonist ketanserin (KET; 18-550 nmol) were injected i.c.v. (10 microliters) and ALF (500 micrograms/kg s.c.) was administered 10 min later. S.c. electrodes were used to record gastrocnemius electromyographic activity. Both MN and DEX dose-dependently and potently antagonized ALF-induced rigidity. ST91 produced shorter-lived, less profound, antagonism of ALF rigidity. PRZ, at the highest dose tested, produced a delayed and modest reduction in ALF rigidity. A large, non-selective, dose of KET incompletely attenuated ALF rigidity. These results lend support to the hypothesis that central opioid and alpha-2 adrenergic receptors mediate opiate-induced muscle rigidity in the rat.

Adrenergic alpha-Agonists↗
PubMed1995

Precursor cells to CD3-intermediate (CD3int) liver mononuclear cells in the adult liver: further evidence for the extrathymic development of CD3int liver mononuclear cells.

Liver mononuclear cells (LMNC) can be divided into CD3-high positive (CD3hi), CD3-intermediate positive (CD3int) and CD3- populations. CD3int LMNC, but not CD3hi LMNC, are considered to be extrathymically derived because they are found in the liver of nude mice and adult thymectomized lethally irradiated bone marrow chimeras. CD3int LMNC express NK1.1 and show a skewed T cell receptor (TCR) V region repertoire with relatively high levels of V beta 8 and V alpha 14 expression, further suggesting that they belong to a different lineage from conventional T cells, which lack NK1.1 expression and V region skewing. Since the liver has been proposed to be a site of extrathymic T cell differentiation in adult mice, we analyzed LMNC for the presence of T cell precursors. CD3- LMNC contained CD4- CD8- cells and CD4lo CD8- cells. Reverse transcription-polymerase chain reaction analysis showed both CD3- populations express the recombination-activating gene -1, which is indispensable in gene rearrangement of TCR and expressed by thymic T cell precursors. Furthermore, when electronically sorted CD3- LMNC were cultured in medium without any feeder cells or exogenously added cytokines for 24 h, CD3int cells, but not CD3hi cells, appeared. These results suggest that the adult liver contains T cell precursors that lack the expression of the CD3/TCR complex, but are strongly committed to differentiate into extrathymic liver CD3int T cells.

Animals↗
PubMed1995

Natural killer cells inhibit the development of autoantibody production in (C57BL/6 x DBA/2) F1 hybrid mice injected with DBA/2 spleen cells.

We investigated the role of natural killer (NK) cells in the development of autoantibody production in which (C57BL/6 x DBA/2) F1 (BDF1) hybrid mice were injected intravenously with spleen cells (SC) from parental DBA/2 mice (treated BDF1 mice). Treated BDF1 mice began to show an increase in serum anti-dsDNA antibody 2 weeks after injection, while the NK activity of their SC transiently increased initially in the first 1 to 2 weeks after injection, but subsequently decreased dramatically. Flow cytometric analysis suggested that this sequential change in NK activity correlated with the absolute number of host-derived NK1.1+ cells in SC from treated BDF1 mice. We demonstrated that the level of anti-dsDNA in serum is directly influenced by the level of NK activity in treated BDF1 mice. Depletion of NK cells by administration of anti-NK1.1 mAb accelerated the development of autoantibody production, whereas augmentation of NK activity by administration of poly-(I:C) inhibited the development of autoantibody production. This inhibitory effect of poly(I:C) was abolished by prior depletion of NK cells. Interestingly, suppression of autoantibody production was seen only when poly(I:C) was administrated within 1 week after injection of parental SC. Last, we demonstrate that adoptive transfer of interleukin-2 (IL-2)-activated NK cells had a protective effect against the development of autoantibody production. These findings imply that NK cells may have a protective role in lupus-like disease especially in its early stage. In addition, it opens up the possibility that adoptive immunotherapy with IL-2-activated NK cells can delay or even prevent the development of autoimmune disease.

Animals↗
PubMed1995

Effect of neonatal thymectomy on murine small intestinal intraepithelial lymphocytes expressing T cell receptor alpha beta and "clonally forbidden V beta s".

Neonatal thymectomy NTX performed on Day 3 of C3H mice causes over a 50% reduction in small intestinal intraepithelial lymphocytes (IEL) expressing the alpha beta T cell receptor (TCR) when analyzed at 10 weeks of age. Furthermore, this reduction is most notable in alpha beta TCR IEL expressing the CD8 alpha homodimer and no Thy 1 marker. This is in direct contradiction to the present theory that alpha beta TCR IEL expressing these markers are thymic independent. Evaluation of V beta expression shows a relative increase in V beta s which are clonally forbidden (V beta s 3, 5, 11), and which is consistent with the extrathymic origin of these particular IEL.

Animals↗
PubMed1995

UMP synthase activity expressed in deficient hamster cells by separate transferase and decarboxylase proteins or by linker-deleted bifunctional protein.

Segments of the human UMP synthase cDNA coding for the orotate phosphoribosyl transferase (OPRT) and orotidylate decarboxylase (ODC) domains of the bifunctional protein UMP synthase were produced by polymerase chain reaction techniques and cloned into a eukaryotic expression vector. The separate OPRT and ODC vectors, along with a selectable marker, were cotransfected into UMP synthase-deficient hamster cells (Urd-C) that require exogeneous uridine for growth. Transfected Urd-C cells surviving selection in media without added uridine were isolated and designated transferase decarboxylase Urd-C (TDU). All of the selected colonies contained DNA corresponding to the OPRT and ODC expression vectors. Two cell lines (TDU3 and TDU5) integrated many more copies of the OPRT and ODC vectors into their genomes compared to the other TDU lines. A 28.6-kDa ODC protein band and a 24.4-kDa OPRT band were detected on western blots with UMP synthase-specific polyclonal antiserum. The OPRT activity of the TDU lines was up to 8.7 times the OPRT activity of control CHL cells, and the ODC activity was up to 12.5 times control levels. Both OPRT and ODC activities in the monofunctional proteins were less heat stable than in the bifunctional UMP synthase protein. The monofunctional OPRT protein was less stable than the ODC protein at 45 degrees C. Growth of transfected cells in 6-azauridine resulted in striking increases in activity and temperature stability for the monofunctional ODC protein. A UMP synthase bifunctional protein was constructed with a deletion of the suspected linker region joining the two catalytic domains. The linker-deleted UMP synthase showed no significant change in either OPRT or ODC activity or temperature stability. The increased stability of the bifunctional protein may be a factor in its evolutionary selection in mammalian cells.

Animals↗
PubMed1995

Photoperiod, early post-natal eye growth, and visual deprivation.

(1) We studied the influence of photoperiod and unilateral lid suture on post-natal ocular growth in two types of White Leghorn chicks previously reported to respond differently to visual deprivation, Truslow and Cornell K chicks. We analyzed the chicks after 2 weeks of rearing, a time period commonly used in neuropharmacological studies of eye growth but much shorter than in most prior studies of photoperiod effects on the chick eye. (2) Altering the photoperiod length significantly influenced the refraction and growth of both open and sutured eyes even at this early time, with differences between the two types of chicks. (3) The most prominent effect on the open eyes was the development of hyperopia with rearing under constant light, a response especially prominent in the Cornell K chicks. In the open eyes under this condition, the anterior chamber shallowed and the vitreous chamber elongated in the axial dimension only, reciprocal changes that resulted in no net alteration of axial length at 2 weeks. A high variability in refraction of open eyes reared with constant illumination suggests the need for a dark period in the regulation of eye growth. (4) Compared to contralateral open eyes, the lid-sutured eyes of both types of chicks developed longer total axial lengths and enlarged vitreous chambers in both axial and equatorial dimensions under each photoperiod. The effects on anterior chamber depth and refraction were complex and differed between the two types of chicks. (5) The responses in open eyes support the notion that growth of the vitrious chamber of the chick eye is differentially regulated in the axial and equatorial dimensions, previously indicated by pharmacological studies. The responses in both open and sutured eyes indicate different control mechanisms for anterior chamber and vitreous cavity growth.

Animals↗
PubMed1995

Quantifying 2-factor phase relations in non-linear responses from low characteristic-frequency auditory-nerve fibers.

Auditory-nerve excitation by two response factors that can be in antiphase has been hypothesized by Kiang (1990) on the basis of non-linear interference in responses to tones (Kiang et al., 1969). The general conditions for antiphasic responses and the relevance of the hypothesis for other auditory stimuli are unknown. Clarification was sought in a systematic modeling study of published data on level-dependent non-linear responses from low characteristic-frequency (CF) auditory-nerve fibers for a broad variety of acoustic stimuli. The MBPNL non-linear I/O model of cochlear frequency analysis (Goldstein, 1990), which incorporates the 2-factor hypothesis, was used to simulate the reported non-linear phenomena. It was found that experiments with paired click stimuli (Goblick and Pfeiffer, 1969) and with octave-band complex tones (Horst et al., 1990), in addition to experiments with single clicks or tones, are sensitive to the phase difference between factors. Surprisingly, the paired-click transient responses require a quadrature phase, while the complex-tone steady-state responses require an antiphase relation. The MBPNL model simulations of all low-CF data surveyed,for simple and complex stimuli, are consistent with a quadrature phase for transient responses and antiphase relation for steady-state responses. It is hypothesized that some adaptive, low-CF, cochlear mechanism, not described by the basic MBPNL model, produces a temporal transition of the '2-factor' response from an initial quadrature relation (tip leading) to a final antiphase relation. New experimental and modeling research guided by this working hypothesis is proposed.

Acoustic Stimulation↗
PubMed1995

Sex differences in chick eye growth and experimental myopia.

Stimulated by reported sex differences in eye size and refraction in humans, we compared refractions and ocular size measurements of male and female chicks. Chicks were reared under a 12-hr light/dark cycle with one eye open and the other occluded by a goggle or lid suture, each well-established means of inducing ipsilateral myopia. While the open eyes of the two sexes emmetropized equally well, both ultrasound and caliper measurements demonstrated that on average males have larger eyes. Although statistically significant for defined populations, the sex differences in open eyes were to small to be diagnostic for individual birds. The visually-deprived eyes of male chicks were more reactive than those of females, especially following deprivation by a goggle. Consistently, the anterior chamber of visually-deprived eyes of males was deeper than those of the females regardless of the means of impairing vision. With a goggle, males also developed more myopia and a deeper vitreous chamber than females similarly occluded. When goggles were removed, rapid recovery occurred in 2 weeks irrespectively of sex.

Animals↗
PubMed1995

Ciliary ganglion choline acetyltransferase activity in avian macrophthalmos.

While present evidence fails to support an etiologic mechanism for myopia based on accommodation or choroidal blood flow, atropine exhibits anti-myopia activity in many species. Accordingly, we studied choline acetyl transferase (ChAT) activity in the ciliary ganglion, uvea and retina of chicks with experimental macrophthalmos to identify a potential pathway for the moderation of eye growth by cholinergic neurons. Following unilateral lid suture or goggle, chicks were reared for 1 week under one of four lighting conditions known to induce macrophthalmos or myopia. Ocular tissues and ciliary ganglia were assayed for ChAT activity by measuring the conversion of 14C-acetyl CoA to 14C-acetylcholine. For some chicks, the goggles were removed at 1 week, and ChAT activity was measured 2 or 7 days later. Depending on the rearing condition, ciliary ganglion ChAT activity was depressed from 16 to 28% ipsilateral to the lid suture; enzyme activity also was reduced in the choroid of visually deprived eyes under most conditions. In contrast, lid suture resulted in no consistent trend in ChAT activity in either the anterior uvea or retina. For chicks wearing a unilateral goggle and reared under a 12:12 hr light/dark cycle, ChAT activity was depressed in the ciliary ganglion, anterior uvea and choroid on the visually deprived side. Following goggle removal to allow recovery from myopia. ChAT activity in the ciliary ganglion and uvea was returned toward that of the control side. The ciliary ganglion may participate in a neural pathway influencing the development of form-deprivation myopia.

Animals↗
PubMed1995

Extrathymic and thymic origin of murine IEL: are most IEL in euthymic mice derived from the thymus?

Although an abundance of literature supports the hypothesis that murine intestinal intraepithelial lymphocytes (IEL) can develop extrathymically, whether most IEL in euthymic mice ar extrathymically derived is unknown. Recent evidence, however, suggests that the development of most IEL in euthymic mice is influenced either directly or indirectly by the thymus. While some evidence suggests that the thymus can influence the extrathymic development of IEL through time-derived factors, clearly a substantial portion (if not most) of the IEL in euthymic mice are derived directly from the thymus. The ability of the thymus to generate IEL depends on the age of the thymus, as fetal/neonatal thymus up to approximately 2 weeks of age generates a totally different subset of IEL than the adult thymus. These results suggest that the IEL generated from the fetal early neonatal thymus recognize a different antigen than the IEL generated from the adult thymus. The former probably recognizes self-antigen and the later recognizes bacterial antigen.

Aging↗
PubMed1995

Interleukin-1 induces insulin-like growth factor binding protein-3 gene expression and protein production by Leydig cells.

Interleukin-1 (IL-1) is a potent inhibitor of Leydig cell function. IL-1 blocks human CG-induced cAMP and testosterone formation, as well as cytochrome P450 side-chain cleavage messenger RNA (mRNA) expression. IL-1 also decreases insulin-like growth factor-I (IGF-I) mRNA levels in Leydig cells. The effects of IGF-I are modified by IGF binding proteins (IGFBPs). In the present study, we evaluated the effects of IL-1 on IGFBP expression. Purified Leydig cells from adult rats were cultured with 0.1% heat-inactivated fetal bovine serum in Dulbecco's modified Eagles' medium/F12. Culture medium was changed to serum-free Dulbecco's modified Eagles' medium/F12 after 24 h and IL-1 beta (0.1-10 ng/ml) was added. Treatment of Leydig cells with IL-1 beta (10 ng/ml) for 2, 4, and 6 h resulted in a progressive induction of IGFBP-3 expression without affecting IGFBP-2 or IGFBP-4 mRNA levels. IL-1 beta in concentrations of 0.1, 1, and 10 ng/ml caused a 1.5-, 4-, and 6.5-fold induction of IGFBP-3 expression, respectively, whereas IGF-I mRNA levels were decreased in a dose-dependent manner. IL-1 beta increased the average transcription rate of IGFBP-3 by 3.3-fold. The t1/2 for IGFBP-3 mRNA was 2.07 h and was not affected by the treatment with IL-1 beta (2.21 h). The immunoblot of cell-conditioned media showed that the basal level of IGFBP-3 protein was low and IL-1 beta caused a dose-dependent increase in the production of IGFBP-3. These results indicate that IL-1 beta increases IGFBP-3 levels by increasing the rate of transcription rather than by changing the stability of IGFBP-3 mRNA. The addition of cycloheximide markedly inhibited IL-1 beta-induced IGFBP-3 mRNA levels. However, IL-1 beta was able to induce IGFBP-3 mRNA levels even in the presence of cycloheximide. This suggests that de novo protein synthesis may not be required for induction of IGFBP-3 mRNA by IL-1 beta. In conclusion, IL-1 beta inhibits IGF-I but increases IGFBP-3 expression in Leydig cells, and this may contribute to the inhibitory effects of IL-1 beta on Leydig cell steroidogenesis.

Animals↗
PubMed1995

The CERAD experience, Part VIII: Neuroimaging-neuropathology correlates of temporal lobe changes in Alzheimer's disease.

We compared premortem neuroimaging findings with neuropathologic evidence of temporal lobe atrophy in 20 patients with Alzheimer's disease (AD) confirmed by autopsy. There were significant correlations between temporal horn enlargement observed by neuroimaging and hippocampal atrophy at autopsy, and between the overall cerebral atrophy severity on neuroimaging and scores on the Mini-Mental State Examination. This report confirms previous studies correlating temporal lobe atrophy on neuroimaging with a clinical diagnosis of AD, although more precise neuroimaging techniques are needed for use in multicenter studies of AD.

Alzheimer Disease↗
PubMed1995

Transduction of LacZ gene into leukemia cells using viral vectors of retrovirus and adenovirus.

Recent developments in gene therapy techniques enable us to introduce new genetic information into hematopoietic cells. Among the various techniques, we focused on two viral vector systems, one using a retrovirus and the other an adenovirus. By using an adenoviral vector we could transduce and highly express bacterial beta-galactosidase (LacZ) gene under the control of the CAG (cytomegalovirus enhancer with chicken beta-actin promoter) promoter in various hematopoietic cells, although the expression persisted for only two weeks. The retroviral vector (MFG) could transduce the LacZ gene into hematopoietic cells almost as well as the adenoviral vector using the repetitive infection protocol. The retroviral system could maintain the expression of transduced cells quite longer than the adenoviral system. Differential use of these two vector systems may be helpful for the gene transduction into various kinds of hematopoietic cells (Lin et al., manuscript in preparation).

Actins↗
PubMed1995

A severe case of diversion colitis with large ulcerations.

Diversion colitis is an inflammatory condition that develops in the excluded segment of colon after surgical diversion. Inflammatory changes include aphthous-type ulcerations, crypt abscesses, and mucosal friability. These features may be seen in other inflammatory diseases of the colon, making diagnosis difficult. Even though symptoms such as cramping pain, bleeding, and mucous discharge have been described with diversion colitis, most cases are asymptomatic. In this article we report a patient who presented with sepsis secondary to severe diversion colitis with several large (2-4 cm in diameter), deep ulcerations and air in the colonic wall, requiring colectomy.

Colectomy↗
PubMed1994

Amelioration of acute graft-versus-host disease and re-establishment of tolerance by short-term treatment with an anti-TCR antibody.

We investigated whether tolerance can be re-established in mice with graft-vs-host disease (GVHD) by using a short-term, T cell-depleting treatment with an anti-TCR-alpha beta mAb. GVHD was induced in 950-rad-irradiated AKR mice (H-2k, Mls-1a) by injecting 5 x 10(6) T cell-depleted bone marrow cells together with either 10(7) or 2 x 10(6) lymph node (LN) cells from BALB/c mice (H-2d, and Mls-1b). AKR mice that received 10(7) LN cells exhibited a severe form of acute GVHD, in which all mice died by day 60. In this severe form of GVHD, treatment with anti-TCR-alpha beta mAb completely ameliorated the induction of GVHD when initiated on day 0 (a total of 800 micrograms/mouse administered on days 0,5, and 10). When the same protocol was begun on day 10, it had no therapeutic effect. However, this delayed treatment with anti-TCR-alpha beta mAb was very effective in reversing a less severe form of GVHD that was induced by the injection of 2 x 10(6) donor LN cells. Recipient mice given prophylactic anti-TCR-alpha beta treatment achieved host-specific tolerance in association with clonal deletion of host Mls-1a-reactive V beta 6+ T cells. In contrast, spleen cells from recipient mice that recovered from the mild form of GVHD as a result of the delayed anti-TCR-alpha beta treatment contained a considerable proportion of the V beta 6+ T cells, despite the healthy appearance of these mice. A MLR assay revealed that the spleen cells from these mice responded well to Mls-1a Ag but not to H-2k Ag, in contrast with the apparent responses of spleen cells from untreated GVHD controls to both Ags. In addition, cells from the anti-TCR-alpha beta-treated mice exhibited a specific reduction in cytotoxicity against AKR blasts. Collectively, these data indicate that a short-term treatment of mice having GVHD with an anti-TCR-alpha beta mAb, starting even after disease onset, can re-establish host-specific tolerance, at least to the host-histo-compatibility Ag.

Acute Disease↗
PubMed1994

CD3-CD8+ intestinal intraepithelial lymphocytes (IEL) and the extrathymic development of IEL.

Present evidence suggests that a majority of murine CD3+ intraepithelial intestinal lymphocytes (IEL) are extrathymically derived T cells and that these extrathymically derived IEL phenotypically express the CD8 homodimer (CD8 alpha alpha). Recently, CD3- IEL have been reported to express the recombination activating gene (RAG-1), suggesting that precursors to extrathymically derived CD3+CD8+ alpha alpha IEL exist on the intestinal epithelium. To study in detail whether these CD3-IEL can develop into CD3+CD8+ alpha alpha IEL, we analyzed the CD3-IEL subset and found that it can be separated into two subsets, namely CD3-CD8- and CD3-CD8+ IEL. We show that (1) CD3-CD8- IEL are mostly small, non-granular and phenotypically Pgp-1+ IL-2R+ B220-, while CD3-CD8+ IEL are mostly large, granular and phenotypically Pgp-1- IL-2R+ B220+, (2) CD(3-)-CD8+ IEL express the RAG-1 gene, and (3) CD3-CD8-, CD3-CD8+ and CD3+CD8+ alpha alpha IEL, respectively, appear sequentially in normal ontogeny and in bone marrow-reconstituted thymectomized radiation chimeras. In the latter, virtually all CD3+CD8+ alpha alpha IEL expressed the gamma delta T cell receptor (TCR), but not the alpha beta TCR. From this and what is presently known about T cell development, we propose that CD3-CD8+ IEL are an intermediate in extrathymic IEL development and that the development of extrathymically derived IEL occurs at the intestinal epithelium from CD3-CD8- to CD3-CD8+ to CD3+(gamma delta TCR)CD8+ alpha alpha.

Animals↗