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Biomedical subjects

J Lin

Publications and source records attributed to J Lin.

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

[Measurement of respiratory muscle performance in patients with chronic obstructive pulmonary disease].

Respiratory muscle performance is measured in terms of strength and endurance. A RMSE-1 type measuring system for evaluation of respiratory muscle strength (RMS) and endurance (RME) has been developed and tested in normal subjects and patients with stable chronic obstructive pulmonary disease (COPD). The results showed that there was no significant difference between normal subjects and stable COPD patients in RMS measured as maximum inspiratory pressure (MIP) and maximum expiratory pressure (MEP). The maximum load (Load(m)), mean mouth pressure at maximum load (Pmean), and the maximum sustainable inspiratory pressure (SIP(m)) as % MIP (SIP(m)/MIP) were taken as measure of RME. All measures of RME in COPD group were much lower than those in the normal. The measurement of RME can be used to evaluate the effect of respiratory muscle training and direct the respiratory rehabilitation in COPD patients.

Adult↗
PubMed1994

CTLA4Ig prolongs allograft survival while suppressing cell-mediated immunity.

T cell activation is the result of antigen-specific interactions with the TCR/CD3 complex and costimulation via other T cell surface receptors. Prevention of costimulation can result in clonal anergy. CTLA4Ig is a fusion protein that binds with high-affinity to the B7/BB1 ligand and blocks the interaction of this ligand with CD28 and CTLA4. We explored the immunosuppressive effects of CTLA4Ig in a murine nonvascularized heterotopic cardiac transplant model and in a model of cell mediated immunity. CTLA4Ig administered in vivo for two days at the time of transplantation resulted in significant prolongation of allograft survival (55 +/- 2.0 vs. 12.2 +/- 0.5 days for control, P < 0.03). Administration at later times or to previously primed animals produced no prolongation of graft survival. CTLA4Ig administered during in vivo immunization to the hapten TNP suppressed the contact sensitivity response and inhibited the subsequent in vitro generation of secondary TNP-specific CTL. CTLA4Ig administered in vivo had no effect on subsequent primary alloantigen-specific CTL or MLR responses--however, when added to culture the fusion protein inhibited the MLR response by 80%, but not the alloantigen-specific CTL response. CTLA4Ig inhibited CD4+ and CD8+ proliferative and cytokine responses to alloantigen. Flow cytometry showed no changes in distribution of subpopulations of T cells. These results confirm the immunosuppressive activity of CTLA4Ig in vivo in an allograft model and show that both CD4+ and CD8+ T cells are suppressed by CTLA4Ig. The most efficacious time of administration is during priming of the immune response at the time of antigen presentation.

Abatacept↗
PubMed1994

Several hydrophobic amino acids in the p53 amino-terminal domain are required for transcriptional activation, binding to mdm-2 and the adenovirus 5 E1B 55-kD protein.

The p53 tumor suppressor gene product is a transcriptional activator that may be associated with its ability to suppress tumor cell growth. The acidic amino terminus of the p53 protein has been shown to contain this trans-activation activity as well as the domains for mdm-2 and adenovirus 5 E1B 55-kD protein binding. An extensive genetic analysis of this amino-terminal p53 domain has been undertaken using site-specific mutagenesis. The results demonstrate that the acidic residues in the amino terminus of p53 may contribute to, but are not critical for, this trans-activation activity. Rather, the hydrophobic amino acid residues Leu-22 and Trp-23 of human p53 are both required for trans-activation activity, binding to the adenovirus E1B 55-kD protein and the human mdm-2-p53 protein in vitro. In addition, hydrophobic residues Leu-14 and Phe-19 are crucial for the interactions between p53 and human mdm-2 (hdm-2). Hydrophobic residues Trp-23 and Pro-27 are also important for binding to the adenovirus 5 (Ad5) E1B 55-kD protein in vitro. These mutations have no impact on the ability of the p53 protein to bind to a p53-specific DNA element. These results suggest that 2-4 critical hydrophobic residues in the amino-terminal domain of the p53 protein interact with the transcriptional machinery of the cell resulting in transcriptional activation. These very same hydrophobic residues contact the hdm-2 and Ad5 E1B 55-kD oncogene products.

Adenovirus E1B Proteins↗
PubMed1994

Anti-CD2 mAbs suppress cytotoxic lymphocyte activity by the generation of Th2 suppressor cells and receptor blockade.

The mechanism by which anti-CD2 mAbs inhibit hapten-specific and alloantigen specific CTL was explored. In vivo administration of alpha-CD2 mAbs resulted in 80 to 100% inhibition of alloantigen specific CTLs. Mixing cells from control animals with cells from alpha-CD2-treated groups demonstrated transferable suppression of CTL (40-67% suppression). These suppressor cells were CD4+CD8- and associated with increased IL-4 and TGF-beta in culture as compared with controls. Anti-CD2 mAbs added at the initiation of culture resulted in 60 to 72% inhibition of trinitrophenyl-CTL, whereas mAbs added at the time of assay resulted in less than 50% inhibition of trinitrophenyl-CTLs. F(ab')2 and Fab alpha-CD2 produced inhibition similar to intact mAbs when added at the time of the lytic assay, whereas both produced only modest inhibition in vivo or when added at the initiation of culture. Alloantigen-specific CTLs were not affected by Ab addition to either culture or assay. The immunosuppressive effects were generalizable because a panel of alpha-CD2 mAbs were all comparably effective in suppressing hapten-specific CTLs when administered in vivo. The results demonstrate that the inhibitory effects are the result of blockade of receptor adhesion function during Ag priming or target recognition, Fc-related effects, and the generation of a negative regulatory, CD4+CD8-, IL-4- and TGF-beta-producing TH2 suppressor T cell.

Animals↗
PubMed1994

Growth suppression and toxicity induced by caffeic acid phenethyl ester (CAPE) in type 5 adenovirus-transformed rat embryo cells correlate directly with transformation progression.

The active component of the honeybee hive product propolis, caffeic acid phenethyl ester (CAPE), induces a selective growth suppressive and toxic effect toward cloned rat embryo fibroblast cells transformed by adenovirus type 5 (Ad5) or the Ad5 E1A transforming gene versus untransformed cloned rat embryo fibroblast cells (Z-z. Su et al., Mol. Carcinog., 4: 231-242, 1991). The present study was conducted to determine whether CAPE-induced growth suppression/toxicity was a direct result of expression of the Ad5 E1A and E1B transforming genes or a consequence of the action of these genes resulting in the transformed state. For this investigation we used somatic cell hybrids and 5-azacytidine-treated Ad5-transformed rat embryo cells that display different stages of expression of the transformed phenotype. This series of cell lines has permitted us to determine whether expression of the transformed state and the stage of transformation progression regulates CAPE sensitivity. Evidence is presented indicating that sensitivity to CAPE is directly determined by the state of expression of the transformed progression phenotype, as opposed to simply the expression of the Ad5 E1A and E1B transforming genes. These results provide further evidence that CAPE may represent a unique compound that can specifically target progressed transformed cells for growth suppression and toxicity. An understanding of the mechanism underlying this selective effect of CAPE could result in the identification of important biochemical pathways mediating cellular transformation and progression of the transformed state.

Adenovirus E1A Proteins↗
PubMed1994

Anti-CD2 monoclonal antibodies synergize with FK506 but not with cyclosporine or rapamycin to induce tolerance.

CsA, FK506, and rapamycin prolong allograft survival; however, each has significant associated side effects at therapeutic doses. Anti-CD2 mAbs also prolong survival but without toxicity. We tested whether alpha CD2 mAbs in combination with subtherapeutic immunosuppression could prolong allograft survival in a synergistic fashion. C57BL/6 (H-2b) mouse hearts were transplanted to CBA (H-2k) mice in a heterotopic, non-vascularized cardiac allograft model. Recipients received immunosuppressants intraperitoneally for 14 days and/or alpha CD2 mAb intravenously for 2 days starting at the time of grafting. Survival was determined by electrocardiogram monitoring. Anti-CD2 alone prolonged survival to 22.4 +/- 1.0 days versus 13.4 +/- 0.5 days for untreated controls (P < 0.05), while low dose FK506 minimally prolonged survival to 16.7 +/- 0.7 days (P < 0.057). However, FK506 plus alpha CD2 resulted in synergistic prolongation of graft survival to 28.0 +/- 2.1 days. Several doses of CsA and rapamycin in combination with alpha CD2 did not prolong survival over alpha CD2 administered alone. A 60-day course of low dose FK506 plus alpha CD2 resulted in indefinite graft survival (> 165 days). These animals were tolerant since they accepted a second donor-specific graft. CTL and MLR activity in long-term recipients were normal to both donor-specific and third party alloantigen. The combination of alpha CD2 with low dose FK506 is synergistic in prolonging cardiac allograft survival, while combinations with CsA and rapamycin are not. Continuous administration of low dose FK506 plus alpha CD2 results in a state of tolerance. This suggests that FK506 acts at a different locus in allograft immunity compared with the other immunosuppressants and this may be related to the alternative CD2 T cell activation pathway.

Animals↗
PubMed1994

Affinity labeling and measurement of DNA-induced conformation change in RNA polymerase II.

The inhibition of RNA polymerase II by 8-azido-2'-O-(1-naphthalenesulfonyl)- ATP (AN-ATP) was found to be reversible in the dark and competitive with ATP, with KI = 2.2 +/- 0.2 microM and KATP = 20 +/- 0.5 microM, but noncompetitive with CTP and GTP, with dissociation constants KCTP = 4.4 +/- 0.4 microM and KGTP = 19.4 +/- 0.7 microM. Under UV irradiation the enzyme was irreversibly labeled by AN-[alpha-32P]ATP. A linear plot of the relative specific activities of labeled enzyme samples after gel filtration vs the number of labels per enzyme molecule shows that each covalent label completely inactivates an enzyme molecule. Therefore the labeling has maximal specificity at an essential specific ATP site which is not the substrate-binding site for the polymerization reaction. The fluorescent AN-ATP-labeled enzyme, with absorbance maximum at 310 nm and emission maximum at 370 nm, can still bind noncovalently a second ligand, 2'-O-dansyl-ATP, with absorbance maximum at 365 nm and emission maximum at 560 nm, at the substrate-binding site. Measurement of energy transfer between the two fluorescent labels gave R = 23.8 +/- 0.4 A as the average distance between them and Kd = 31 +/- 0.1 microM for the bound 2'-O-dansyl-ATP in the absence of DNA template. The addition of either thymus DNA or poly[d(A-T)] to the system changed these values to R = 25.6 +/- 0.4 A and Kd = 53 +/- 0.4 microM. These results indicate that the binding of RNA polymerase II to DNA template triggers a conformation change in the enzyme molecule.

Adenosine Triphosphate↗
PubMed1994

Topology of the Neurospora plasma membrane H(+)-ATPase. Localization of a transmembrane segment.

The Neurospora plasma membrane H(+)-ATPase is a polytopic integral membrane protein. To localize transmembrane segments, mutants were constructed that contained the amino and carboxyl termini of the H(+)-ATPase with putative transmembrane segment. A stretch of amino acid residues from yeast invertase that has three consensus N-linked glycosylation sites was placed carboxyl terminal of the putative transmembrane segment. RNA transcripts of these mutants were translated in a Neurospora in vitro system that was supplemented with microsomes from Neurospora. By the criteria of glycosylation of the polypeptide chain, resistance to extraction at pH 11.5, and protection from proteinase K digestion, only one transmembrane segment could be identified within the amino acid residues 272-314 of the primary sequence of the H(+)-ATPase.

Amino Acid Sequence↗
PubMed1994

Anti-CD2 receptor and anti-CD2 ligand (CD48) antibodies synergize to prolong allograft survival.

Indefinite graft survival was obtained with murine cardiac allografts using the combined administration of monoclonal antibodies (mAbs) directed against the receptor ligand pair CD2-CD48. Although each antibody could prolong graft survival when given alone, neither resulted in the indefinite graft survival seen with the combination. Combined mAb administration is associated with inhibition of T cell priming and help and subsequent cytotoxic T lymphocyte generation. This indicates that the interaction between CD2 and its ligand is important for antigen priming and recognition, and combined mAbs may prove to be a useful therapeutic regimen for transplantation.

Animals↗
PubMed1994

Serum thrombomodulin. A novel marker of disease activity in systemic lupus erythematosus.

OBJECTIVE: Soluble thrombomodulin (sTM), a proposed serum marker of endothelial cell injury, was investigated as a parameter of disease activity in patients with systemic lupus erythematosus (SLE). METHODS: Levels of sTM were determined by enzyme-linked immunosorbent assay. Disease activity was assessed using 3 established scoring systems: the American College of Rheumatology (ACR), the New York Hospital for Special Surgery (NYHSS), and the Systemic Lupus Activity Measure (SLAM) systems. RESULTS: A close correlation was found between sTM levels and disease activity as assessed with all 3 scoring systems: r = 0.52 by the ACR, 0.75 by the NYHSS, and 0.82 by the SLAM. CONCLUSION: We found that sTM is a sensitive serologic marker of organ involvement in patients with SLE. Furthermore, sTM may prove to be an important marker for vasculitis in general.

Adolescent↗
PubMed1994

A modified free gracilis flap in the rat.

We present in this paper the use of a combined neurovascularized flap of gracilis muscle and inguinal skin in the rat with the femoral vessels and obturator nerve serving as the pedicles. The epigastric, saphenous, and muscular branch vessels arising from the femoral vessels were preserved, and a portion of adductor magnus muscle was included in the flap to protect the delicate muscle vessels at their origins. The inguinal skin and muscle flap both had independent blood supplies, thus separate assessment of muscle and skin rejection was possible in the single transplanted "packet." The muscle flap with the reconnected motor nerve regained contractile ability upon nerve stimulation within 30 days after the iso-transplantation. The results suggest that the modified gracilis myocutaneous flap provides an ideal model for transplantation research.

Animals↗
PubMed1994

Hispanic/white differences in dietary fat intake among low educated adults and children.

BACKGROUND: This comparative study tests for ethnic differences in dietary fat consumption in a community-based sample of Hispanic and white adults with low educational attainment (< 12 years of schooling) and a separate sample of their children. METHODS: Data are presented for adults (age 20-64, n = 886) and youths (age 12-19, n = 170) from four California cities who participated in one of four sequential cross-sectional surveys (1981-1990). RESULTS: After adjustment for age, sex, city of residence, and time of survey, white adults were significantly (P < 0.03) more likely than Hispanic adults to have eaten high-fat foods in the last 24 hr, such as red meat (75.7% vs 68.4%), cured meats, (39.1% vs 25.8%), and cheese (41.4% vs 32.7%). Furthermore, white adults consumed significantly (P < 0.001) more fat, as measured by percentage of calories from total fat (37.7% vs 33.3%) and saturated fat (13.7% vs 11.8%), and consumed significantly less dietary carbohydrate (45.5% vs 49.7%) and fiber (17.1 g vs 26.0 g) than Hispanic adults. Ethnic differences were similar for the youth sample (except for carbohydrates), but were generally not significant. A graded relationship was found between acculturation and dietary measures, where more acculturated Hispanics (English-speaking) were intermediate between less acculturated Hispanics (Spanish-speaking) and whites in their dietary intake. CONCLUSIONS: This study illustrates the high dietary fat consumption of whites with low educational attainment, the increasing fat consumption of Hispanics at higher levels of acculturation, and the need for effective dietary interventions for low educated whites and Hispanics.

Acculturation↗
PubMed1994

Determination of tumour vascularity using selective hepatic angiography as compared with intrahepatic-arterial technetium-99m macroaggregated albumin scan in hepatocellular carcinoma.

A total of 51 patients with hepatocellular carcinoma (HCC) were studied to determine the tumour vascularity as determined by selective hepatic angiography (HAG) and by intrahepatic-arterial technetium-99m-labeled macroaggregated albumin (Tc99m-MAA) scan. The tumour vascularity was graded on the HAG films by an interventional radiologist using a scale ranging from 1 (hypovascular) to 4 (extremely hypervascular). The grades of vascularity on HAG were grade 1 in 5 patients, grade 2 in 13 patients, grade 3 in 24 patients and grade 4 in 9 patients. The tumour vascularity on scintigraphy was determined by quantifying the count rates over the tumour and normal liver areas by an analog/digital gamma-camera, and the resultant tumour-to-normal ratio (T/N ratio) gave a quantitative measure of the vascularity. The range of the T/N ratio was 0.9 to 11.1, with a median of 3.7. There was no correlation between the tumour vascularity grading on HAG and the T/N ratio on the Tc99m-MAA scan (Wilcoxon rank test, P = 0.83). Thus, we conclude that HAG cannot reveal the true vascularity nor reflect the T/N ratio in HCC.

Angiography↗
PubMed1994

Oxidation of dibenzothiophene catalyzed by heme-containing enzymes encapsulated in sol-gel glass. A new form of biocatalysts.

We have encapsulated several hemoproteins in the sol-gel glass to catalyze the oxidation reaction of dibenzothiophene (model for organic sulfur compounds in coal) with hydrogen peroxide. In addition to cytochrome c and myoglobin, which have previously been encapsulated in sol-gel glasses, two other hemoproteins, horseradish peroxidase and bovine blood hemoglobin, have now been successfully immobilized in sol-gel media with the retention of their spectroscopic properties. All four hemoproteins studied also demonstrate similar catalytic activities toward the oxidation of dibenzothiophene as compared with the results obtained with the proteins in solution. In the case of encapsulated cytochrome c, the more water-soluble S-oxide was obtained with much higher selectivity over the less water-soluble sulfone (S-oxide/sulfone = 7.1) as compared to what was obtained in the aqueous/organic medium (S-oxide/sulfone = 2.3). Because of the advantage of easy separation of the encapsulated proteins from the liquid reaction mixture, it is clear from these studies that the immobilization of active hemoproteins in the solid glass media could serve as more practical biocatalysts.

Catalysis↗
PubMed1994

DNA inoculation as a novel vaccination method against human retroviruses with rheumatic disease associations.

There are a number of rheumatologic manifestations of human retroviral infections associated with human immunodeficiency virus type I (HIV-I) and the human T-cell leukemia virus type I (HTLV-I) including arthritis, Sjøgren's syndrome-like symptoms as well as other varied autoimmune phenomena. Infection with HTLV-1 may be directly involved in the etiology and/or pathogenesis of an arthritic condition similar to rheumatoid arthritis. We have been characterizing a new vaccination strategy against human retroviral infections, designated DNA inoculation. This procedure involves the intramuscular injection of DNA plasmids which express specific human retroviral antigens. This technique results in the development of humoral and cellular immune responses against these proteins. Specifically, this method has been successfully used to develop immune responses against HIV-I and HTLV-I. The availability of rat and rabbit infection models for HTLV-I, coupled with the successful development of immune responses in these animals after DNA inoculation with an HTLV-I envelope expressing plasmid, will allow the efficacy of this vaccination technique to be evaluated with protection against in vivo viral challenge as an endpoint.

Animals↗
PubMed1994

Regulation of B-cell activation by CD45: a question of mechanism.

Recent studies have demonstrated that the protein tyrosine phosphatase CD45 plays an integral role in regulation of B-cell function. Most notably, expression of this phosphatase is required for activation of B lymphocytes and entry into the cell cycle. Here, Louis Justement and colleagues review current information concerning the function of CD45 in the B cell. The discussion focuses on two questions that are of central importance: what are the physiological substrates for CD45 and how does reversible tyrosine phosphorylation affect their function?

Animals↗
PubMed1994

Cytoreductive surgery for hepatocellular carcinoma.

A prospective study was conducted on 26 patients for cytoreductive surgery of inoperable hepatocellular carcinoma. These patients underwent cytoreduction with liver resection, cryosurgery, microwave tissue coagulation and/or absolute alcohol injection. In-hospital mortality was 7.7%. The symptomatic relief and quality of survival were excellent. The median survival of patients after cytoreduction was 10.0 months and the survival was much better than those of 26 patients matched by sex, age, tumour size, Child-Pugh grading and Karnofsky scores who received systemic chemotherapy during the same period of the study (log rank test, P = 0.0001). There was no statistical difference between the survival curves of those patients who received (19 patients) and those who did not receive (7 patients) additional treatment by chemotherapy or selective internal radiation therapy after cytoreduction. This suggests that the gained survival benefit could have been derived mainly from the cytoreductive surgery rather than the additional treatments.

Adolescent↗