Biomedical subjects
Publications and source records attributed to T Lin.
In this paper, a new algorithm based on Voxel Model is proposed. This algorithm combines the advantages of surface rendering and direct volume rendering. In the process of 3D reconstruction, OpenGL graphic standard and hardware accelerator can be used. By doing so, better reconstruction, result and fast speed can be achieved. Also, it is simple to turn this algorithm into programs.
This paper discusses the necessity of gateway between WWW and DICOM, shows the method of the implementation and the result. It brings forward a new way in which doctors interact with PACS and medical image device such as CT, MRI, ultrasonic, etc. It points out that the gateway between WWW and DICOM is a kind of transition between appropriative standard and general standard. This kind of transition will bring convenience to telemedicine information system and integrated medical information system.
Results are presented showing the ability to obtain C-terminal sequence information from peptides by multiple stages of mass spectrometry. Under typical low-energy collision-induced dissociation conditions of quadrupole ion trap and ion cyclotron resonance mass spectrometers, lithium- and sodium-cationized peptides dissociate predominantly by reaction at the C-terminal peptide bond or an adjacent bond. For the majority of cases studied, the dominant reaction is a rearrangement process that results in the loss of the C-terminal residue and formation of a product ion that is one amino acid shorter than the original peptide ion. Using the multistage MS/MS capabilities of quadrupole ion trap and ion cyclotron resonance mass spectrometers, a subsequent stage of MS/MS can be performed to determine the identity of the new C-terminal residue. Up to eight stage of MS/MS have been performed with both quadrupole ion trap and ion cyclotron resonance mass spectrometers. In general, the same dissociation pathways are observed with both instruments, although occasionally there are significant differences in the branching ratios of competing pathways.
In vitro studies have demonstrated that intestinal intraepithelial lymphocytes (IEL) are constitutively cytotoxic; however, the mechanism and target of their cytotoxicity are unknown. Apoptosis of intestinal epithelial cells (IEC) and an increase in IEL numbers are classical signs of intestinal graft-versus-host disease (GVHD), although whether IEL can mediate IEC apoptosis directly in GVHD is unclear. Recent evidence suggests that target epithelial organ injury observed in GVHD is predominantly Fas-mediated; therefore, we investigated the possibility that IEL induce apoptosis of IEC through a Fas-mediated mechanism. Here, we demonstrate that the IEL isolated from normal mice readily display potent Fas ligand (FasL)-mediated killing activity after CD3 stimulation, and that IEC express Fas, suggesting that IEC are potential targets for FasL-mediated killing by IEL. In vitro, IEL isolated from GVHD mice have markedly increased FasL-mediated killing potential and are spontaneously cytolytic toward host-derived tumor cells predominantly through a Fas-mediated pathway. In vivo transfer of IEL isolated from GVHD mice induced significantly more IEC apoptosis in F1 wild-type mice than in Fas-defective F1lpr mice. Thus, these results demonstrate that FasL-mediated death of IEC by IEL is a major mechanism of IEC apoptosis seen in GVHD.
The oculocerebrorenal syndrome of Lowe (OCRL) is a rare X-linked disorder with a severe phenotype characterized by congenital cataracts, renal tubular dysfunction and neurological deficits. The gene has been characterized and mutations have been identified in patients. Owing to the allelic heterogeneity exhibited by this gene, prenatal diagnosis by molecular analysis is limited to families in which the mutation is already known or in which linkage is informative. A more generally applicable diagnostic test would be valuable for families at risk for Lowe syndrome. Since ocrl1 is now known to encode a phosphatidylinositol 4,5-bisphosphate 5-phosphatase (Ptdlns(4,5)P2 phosphatase), we assessed whether biochemical testing could be used for prenatal diagnosis. We report here the first case of prenatal diagnosis for Lowe syndrome by measuring phosphatidylinositol 4,5-bisphosphate 5-phosphatase activity in cultured amniocytes.
Lowe syndrome (OCRL) is an X-linked disorder involving the eyes, kidney, and nervous system that is caused by loss of function in the OCRL1 gene. OCRL1 contains 24 exons (23 of which are coding) and encodes a 105-kDa enzyme with phosphatidylinositol 4,5 bisphosphate (PtdIns[4,5]P2) 5-phosphatase activity. We published previously (1,2) 13 different mutations in 10 families. Four are missense other 8 mutations in 10 families. Four are missense mutations in highly conserved PtdIns (4,5)P2 5-phosphatase caused by nonsense mutations, and three others are premature terminations caused by frameshift mutations. One frameshift, a GT deletion in exon 21, has been observed previously in two unrelated Lowe syndrome patients, suggesting that it may be a relative "hotspot" for mutation in a disorder marked otherwise by allelic heterogeneity. We have also seen two other recurrent mutations. One is a nonsense mutation CGA > TGA in exon 2 observed in two patients and the second is a missense mutation CGA > CAA in exon 15 present in two unrelated patients. These 21 distinct mutations we have found in 25 Lowe syndrome patients occur in only 9 of the 24 exons: 10, 12, 13, 14, 15, 18, 19, 21, and 22. Interestingly, missense mutations have occurred only in exons 12 through 15 in highly conserved residues among the phosphatidylinositol 5-phosphatases. These observations suggest useful strategies for mutation screening in OCRL.
Depriving the eyes of neonatal animals of form vision induces axial eye elongation and ipsilateral myopia. We studied one-year-old chickens, an age at which full body growth has been attained, to learn if form deprivation myopia can develop at a later stage. We found that ocular reactivity to visual form deprivation continues in one-year-old chickens; but both the growth stimulation and the myopic shift in refraction are attenuated compared with newly hatched birds. Neurochemical changes in visually deprived eyes of one-year-old chickens parallel those in newly hatched chicks: ipsilateral decreases in retinal dopamine and in the activity of ciliary ganglion and uveal choline acetyltransferase. These findings strengthen the relevance of the form deprivation model to more common human myopia and suggest a common eye growth control mechanism at both ages.
Fas (CD95) and Fas ligand (FasL) play major roles in staphylococcal enterotoxin B (SEB)-induced peripheral deletion of Vbeta8+ T cells. We found that peripheral deletion was defective in radiation chimeras with non-functional tissue FasL, regardless of the FasL status of the bone marrow-derived cells. SEB induced a dramatic upregulation of FasL expression and function in nonlymphoid cells of liver and small intestine. This effect was resistant to inhibition by cyclosporin A, which also failed to inhibit peripheral deletion. In SCID animals nonlymphoid tissues did not express FasL in response to SEB unless transplanted lymphocytes were present. Thus, some immune responses induce FasL in nonlymphoid tissues, which in turn kills activated lymphocytes, leading to peripheral T cell deletion.
The effect of fibre addition on the flexural strength of a resin was studied. A provisional material (ALIKE; GC America Inc.) was used as the control and resinous matrix. Silane treated glass fibre was selected for the reinforcing treatment. In order to determine the geometric influence on the strength, ordered fibres (1 w/o) were immersed within a resinous matrix in four different locations. In addition, randomly dispersed fibres, 5 mm in length, were blended at 1 w/o up to 8 w/o with acrylic powder and moulded into rectangular specimens (34 mm x 9 mm x 8 mm) with P:L = 2:1. Ten specimens were prepared for each group. A three-point flexural test was run using a span of 25 mm at a rate of 5 mm/min. The strength values were collected and analysed with ANOVA and Scheffe tests. The strengths of the specimens with orientated fibre addition ranged from 49.4 (s.d. = 5.7) to 64.5 (6.7) MPa and the control was 54.3 (4.0) MPa. In the dispersed groups, the strengths obtained ranged from 55.9 (5.9) to 87.3 (7.9) MPa. The results disclosed that inclusion of orientated fibres horizontally on the tension side of the specimens significantly improved the flexural strength compared with the control (P < 0.05). An optimal strength was obtained in the group of provisional resin containing 5 w/o dispersed fibre. Incorporation of glass fibres significantly improved the flexural strength of the resin and the dispersed method is more efficient than the orientated inclusion method.
OBJECTIVES: To compare speech recognition performance in Chinese-speaking cochlear implant patients with a speech processor program selected by the clinical audiologist in Taiwan and with a new speech processor program based on the Washington University clinical procedure developed by Skinner et al. STUDY DESIGN: Six adult Chinese-speaking patients implanted with the Nucleus cochlear implant system participated in this study. METHODS: A fitting procedure developed in 1995 by Skinner et al. at Washington University School of Medicine was used to create a new speech processor program to optimize each patient's hearing in everyday life. Speech tests (vowels, consonants, tones, and words), sound-field thresholds, and a self-report questionnaire were used to evaluate each patient's performance with his or her previous speech processor program and a new one. RESULTS: Four of the six patients had significant changes from the previous to the new speech processor program. These changes were associated with improvement in score on at least one speech test, more sensitive sound field thresholds, and reported improvement in some everyday listening situations on the questionnaire. CONCLUSIONS: These results suggest that use of this procedure with adult cochlear implantees may improve benefit in everyday life. Analysis of the speech test stimuli and patients' responses provides a basis for modification or creation of new Mandarin Chinese speech tests for preoperative and postoperative evaluation of adult cochlear implant patients.
Interferon-gamma (IFNgamma) is an immunomodulating cytokine that has profound effects on reproductive function. IFNgamma inhibits steroidogenesis both in vivo and in vitro. The mechanism by which IFNgamma inhibits Leydig cell steroidogenesis remains unclear. In the present study, we evaluated the effect of IFNgamma on the expression and regulation of the steroidogenic acute regulatory protein (StAR) gene in primary cultures of rat Leydig cells. StAR facilitates the efficient production of steroid hormone by regulating the translocation of cholesterol from the outer to the inner mitochondrial membrane, the site of the cytochrome P450 side-chain cleavage (P450scc) enzyme system that converts cholesterol to pregnenolone. IFNgamma inhibited hCG-induced StAR messenger RNA (mRNA) levels in a dose-dependent manner. The addition of IFNgamma in a concentration of 500 U/ml decreased hCG-induced 3.8- and 1.7-kilobase StAR mRNA by 78% and 70%, respectively. IFNgamma also reduced hCG-stimulated P450scc mRNA levels by 69%. The inhibitory effects of IFNgamma on StAR mRNA levels were confirmed by ribonuclease protection assay. As early as 12 h after the addition of IFNgamma, hCG-induced StAR mRNA levels decreased by more than 44%. To evaluate the effects of IFNgamma on StAR protein levels, Western blot analyses were performed. hCG in a concentration of 10 ng/ml increased StAR protein by 5.6-fold. Treatment of Leydig cells with IFNgamma (500 U/ml) decreased hCG-induced StAR protein by 44%. In contrast, interleukin-1 and murine tumor necrosis factor-alpha reduced hCG-induced P450scc mRNA expression without inhibiting StAR mRNA or protein levels. In conclusion, IFNgamma inhibits Leydig cell steroidogenesis by down-regulating StAR gene expression and protein production.
In the present study, we report the cloning of a gene that is differentially expressed in normal adult rat Leydig cells and whose expression is inhibited by hCG but is induced by interferon-gamma (IFNgamma). DNA sequence analysis identified this gene as rat IFNgamma-inducible protein 10 (IP-10), a member of the -C-X-C- chemokine superfamily of proinflammatory cytokines. High levels of IP-10 messenger RNA (mRNA) were constitutively expressed in freshly isolated and primary cultured Leydig cells. hCG inhibited this expression in a dose-dependent manner. The addition of 1 ng/ml hCG inhibited IP-10 mRNA levels more than 80%. Conversely, IP-10 mRNA levels were markedly increased in response to murine interleukin-1alpha, murine tumor necrosis factor-alpha, and murine IFNgamma by 3.3-, 10-, and 26-fold, respectively. Concomitant addition of murine interleukin-1alpha, murine tumor necrosis factor-alpha, and murine IFNgamma synergistically increased IP-10 mRNA levels by 58-fold. Furthermore, in addition to one previously described rat IP-10 mRNA transcript (1.5 kb), another larger transcript (2.7 kb) was identified by Northern blot in rat Leydig cells. After screening a rat testis complementary DNA library, we obtained a partial structural gene and an intron sequence, which possibly originated from the larger transcript of rat IP-10 mRNA. Histochemical and immunocytochemical staining revealed that purified cells were positive for 3beta-hydroxysteroid dehydrogenase and IP-10, confirming that IP-10 is indeed present in Leydig cells. IP-10 antisense oligonucleotides enhanced basal and hCG-induced testosterone formation. This suggests that endogenous IP-10 has an inhibitory effect on Leydig cell steroidogenesis. In conclusion, IP-10 is expressed in rat Leydig cells and may have paracrine and autocrine effects on testicular function.
Insulin-like growth factor-I (IGF-I) plays an essential role in reproductive function. Leydig cells express specific IGF-I receptors, and IGF-I enhances human chorionic gonadorphin (hCG)-induced testosterone formation. In the present study, we evaluate the effect of IGF-I on the gene expression and protein levels of steroidogenic acute regulatory protein (StAR), the rate-limiting step in steroidogenesis. StAR mRNA is expressed in rat Leydig cells as two major transcripts of 3.8 and 1.7 kb. StAR mRNA levels (both 3.8 and 1.7 kb) were markedly induced about 20-fold by hCG (10 ng/mL). Concomitant addition of IGF-I (50 or 100 ng/mL) and hCG (10 ng/mL) resulted in significant increases in StAR and cytochrome P450 side-chain cleavage (P450scc) mRNA levels, whereas lower doses of IGF-I (1 or 10 ng/ mL) had small effects. Synergistic effects of IGF-I and hCG on StAR mRNA levels were confirmed by ribonuclease protection assay (RPA). IGF-I (100 ng/mL) enhanced hCG- and 20 OH-cholesterol + hCG-induced testosterone formation, whereas the conversions of pregnenolone, 17-OH pregnenolone, dehydroepiandrosterone, and androstenedione to testosterone were not affected. This suggests that the major effect of IGF-I is at the steps of StAR and P450scc, whereas other steroidogenic enzymes are not affected. To evaluate whether increased StAR mRNA levels induced by IGF-I and hCG are associated with increased StAR protein levels, we carried out Western blot analyses. Basal StAR protein levels were low after 24 h in culture. hCG (10 ng/mL) increased StAR protein by 4.5-fold. In the presence of IGF-I (100 ng/mL), hCG-induced StAR protein levels were further increased. In conclusion, our present study demonstrated that IGF-I enhances Leydig cell steroidogenesis by upregulating hCG-induced StAR gene expression and protein production.
The rate-limiting step of steroidogenesis is the transport of the substrate cholesterol from the outer to the inner mitochondrial membrane which involves a cycloheximide-sensitive newly synthesized protein. A protein believed to carry out this function was recently cloned from MA-10 mouse Leydig tumor cells and named the steroidogenic acute regulatory protein (StAR). In the present study, we evaluated the expression and regulation of StAR in primary cultures of rat Leydig cells. StAR mRNA was expressed in Leydig cells as two major transcripts of 3.8 and 1.7 kb and one minor transcript of 1.2 kb. Induction of StAR mRNA transcripts could be detected as early as 30 min after the addition of human choriogonadotropin (hCG) with peak levels attained between 2 and 4 h. hCG in concentrations of 0.1-10 ng/ml caused a dose-dependent increase in StAR mRNA expression. hCG administered at a dose of 10 ng/ml increased the 3.8 kb StAR mRNA level about 14-fold and the 1.7 kb StAR mRNA level about 13.6-fold. hCG-stimulated StAR mRNA was associated with increased StAR protein levels as determined by immunoblot analysis (a 4.5-fold increase). Murine interleukin-1 alpha (mIL-1 alpha) at a concentration of 100 ng/ml inhibited hCG-induced cytochrome P450 side-chain cleavage (P450 scc) mRNA expression and testosterone formation almost completely. Interestingly, mIL-1 alpha had no effect on hCG-induced StAR mRNA or protein levels. Furthermore, mIL-1 alpha (10 ng/ml) decreased conversion of (22R)-hydroxycholesterol to testosterone while the conversion of pregnenolone, 17-hydroxypregnenolone, dehydroepiandrosterone and androstenedione to testosterone were not affected. These results indicate that the major inhibitory effect of IL-1 on Leydig cell function occurs at the level of P450 scc.
OBJECTIVE: To evaluate the efficacy and toxicity of China-made paclitaxel in patients with a variety of advanced malignancies. METHODS: Paclitaxel was administered by i.v. infusion at a dose of 175 mg/m2 in 3-hour every three weeks. All patients received premedication(dexamethasone, diphenhydramine and cimetidine) to prevent allergic reactions. RESULTS: Of 116 patients, 114 patients received 2 to 3 courses of therapy and were evaluable for response. The overall response rate for ovarian cancer was 46.7%, for breast cancer 56.4%, for non-small-cell lung cancer 25.0%, for small-cell lung cancer 66.7%, and for nasopharyngeal cancer 41.7%. Responses were also achieved in patients who had failed to respond to prior chemotherapy, with the overall response rate of 42.9% for ovarian cancer, 57.6% for breast cancer, 33.3% for non-small-cell lung cancer, 25.0% for small-cell lung cancer, and 40.0% for nasopharyngeal cancer. Paclitaxel did not show cross-resistance with doxorubicin and cisplatin. The major toxicity associated with paclitaxel included neutropenia, arthralgia, myalgia, numbness of hands and feet and alopecia. No severe hypersensitivity reactions were observed. CONCLUSION: At the above-mentioned dose and schedule, paclitaxel is effective with tolerable side effects.
To study the relationship between the abnormal behavior of calcium (Ca2+) and the pathogenesis of recurrent aphthous ulceration (RAU) by measuring quantitatively the concentration of platelets' cytosolic free calcium ions ([Ca2+]i) and tissue calcium (Wca2+), the patients with RAU (n = 50) and the healthy volunteers (n = 30) were chosen randomly. Then platelets [Ca2+]i was determined in calcium fluorescent indicator Fura-2/AM loaded washed platelets by spectrofluorophotometer and tissue Wca2+ was measured quantitatively by OCPC autoanalyzer method. The results showed that the concentration levels of platelets [Ca2+]i in patients with RAU in attack stage and attack-free stage were significantly higher than that of the control group (P < 0.01, P < 0.05), and the concentration level of the ulcerous tissue Wca2+ was also obviously higher than that of the normal control group (P < 0.001). There was a significantly positive correlation between the platelets [Ca2+]i and the ulcerous tissue Wca2+ (P < 0.01). The results suggested that the influx disorder and overload of Ca2+ might play an important role in the pathogenesis of RAU.
We have identified two distinct cDNAs encoding the alpha-subunit of pig heart succinyl-CoA synthetase. The derived amino acid sequence of one of these, PHalpha57, is highly similar to the alpha-subunit of the rat liver precursor enzyme. The second cDNA, PHalpha108, was identical throughout its sequence with PHalpha57 except for a stretch of 108 nucleotides which replaced a 57 nucleotide sequence in PHalpha57. Coexpression of either alpha-subunit cDNA with a common pig heart beta-subunit cDNA produced isozymes with GTP-specific enzyme activity. The enzyme produced by the combination of PHalpha57 and the beta-subunit cDNA resembled the "native" enzyme purified from pig heart tissue. In contrast, the expressed enzyme from the combination with PHalpha108 was clearly distinguishable from the native enzyme by, for example, hydroxyapatite chromatography. Moreover, it was now apparent that this isoform had been observed in previous preparations of the native enzyme, but always in very low amounts and, thus, disregarded. We have shown further that the two mRNA transcripts arise from a single gene and are generated by mutually exclusive splicing. The production of the PHalpha108 message involves the use of a non-canonical splice site pair, AT-AA. Finally, we provide evidence for tissue specific regulation in the splicing of the PHalpha108 message.
A rat fibroblast cell line (Rat-1) carrying a temperature-sensitive mutation of v-src was used to determine whether inducible cellular transformation altered the ability of cells to amplify the p-glycoprotein gene in response to colchicine selection. Transformed and nontransformed Rat-1 fibroblasts selected under 4 times the LD50 generated the same number of colchicine-resistant colonies. We next examined colchicine-resistant colonies derived from transformed cells and compared them to colchicine-resistant colonies derived from nontransformed cells. When Rat-1 cells were selected at 35 degrees C (transforming temperature), 7 out of 7 clones exhibited a 3- to 5-fold p-glycoprotein gene amplification. These results contrasted to those found at the nontransforming temperature (40 degrees C); none of the 8 colchicine-resistant clones examined had amplified the p-glycoprotein gene. Thus in Rat-1 cells carrying a temperature-sensitive v-src gene, p-glycoprotein gene amplification was observed at a high frequency only in transformed clones selected at the temperature permissive for v-src activity.