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Biomedical subjects

J Lin

Publications and source records attributed to J Lin.

At least 613 records · Page 34Linked to original sources
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↗
PubMed1994

Endotoxic damage to the stria vascularis: the pathogenesis of sensorineural hearing loss secondary to otitis media?

This study presents animal experiments on endotoxin (lipopolysaccharides: LPS) damage to the inner ear with special reference to the stria vascularis. The experimental group animals (albino guinea pigs) were injected with LPS into the perilymphatic space. Pyrogen-free saline (PFS) was injected into the control group. Strial structural evaluation and hearing tests were carried out before and one, three and five days after treatment. In PFS-treated (control) ears, no significant change was found either in hearing or structure. However, thresholds of N1/P1 were elevated and latencies prolonged in LPS-treated ears. They had severe strial damage mainly to the cellular organelles. The mitochondria became swollen with a disordered, broken, degenerated or absent crest. Secondary lysosomes and autophagosomes increased in number with the presence of medulative inclusions. Na(+)-K(+)-ATPase reactant was obviously diminished. It is concluded that LPS-induced strial ototoxicity produces ion imbalance, causing changes in endolymph composition and energy failure in the organ of Corti and is also responsible for the pathogenesis of inner ear sequelae secondary to otitis media.

Animals↗
PubMed1994

Thalifaberidine, a cytotoxic aporphine-benzylisoquinoline alkaloid from Thalictrum faberi.

From Thalictrum faberi, thalifaberidine [1], a new aporphine-benzylisoquinoline alkaloid, together with four known alkaloids, thalifaramine [2], thalifaricine [3], thalifarazine [4], and thalifaronine [5], were isolated. Thalifaberidine [1] was identified as 6',8-desmethylthalifaberine, and its 1H- and 13C-nmr data were completely assigned through the use of one- and two-dimensional nmr techniques. Thalifaberidine [1], thalifaberine [6], and thalifasine [7] showed cytotoxic activity against several human cancer cell lines, as well as antimalarial activity.

Alkaloids↗
PubMed1994

Treatment of inoperable hepatocellular carcinoma with intrahepatic arterial yttrium-90 microspheres: a phase I and II study.

Eighteen patients with inoperable hepatocellular carcinoma (HCC) were treated with intrahepatic arterial yttrium-90 microspheres. All these patients showed a lung shunting below 15% and a tumour-to-normal ratio higher than 2 as determined by diagnostic technetium-99m macroaggregated albumin (Tc-MAA) gamma scintigraphy. The treatment was given through an arterial port placed during laparotomy. The radiation doses to the liver and tumour were determined intraoperatively with a beta probe and liquid scintillation counting of multiple liver biopsies. The treatment was well tolerated without major complications. In all patients the tumour marker fell to a level which ranged from 41% to 0.2% of the pretreatment level. Tumour regression was found to be dose related. Progressive or static disease occurred in a higher proportion of patients whose tumours received < 120 Gy (P = 0.005). Survival was better in those whose tumours received > 120 Gy (median survival = 55.9 weeks) than those whose tumours received lower doses (median survival = 26.2 weeks). This difference is statistically significant with P = 0.005. We conclude that yttrium-90 microsphere therapy is safe and that tumour response is dose related. A tumour dose of > 120 Gy is recommended.

Adolescent↗
PubMed1994

Lysosome biogenesis requires Rab9 function and receptor recycling from endosomes to the trans-Golgi network.

Newly synthesized lysosomal enzymes bind to mannose 6-phosphate receptors (MPRs) in the TGN, and are carried to prelysosomes, where they are released. MPRs then return to the TGN for another round of transport. Rab9 is a ras-like GTPase which facilitates MPR recycling to the TGN in vitro. We show here that a dominant negative form of rab9, rab9 S21N, strongly inhibited MPR recycling in living cells. The block was specific in that the rates of biosynthetic protein transport, fluid phase endocytosis and receptor-mediated endocytosis were unchanged. Expression of rab9 S21N was accompanied by a decrease in the efficiency of lysosomal enzyme sorting. Cells compensated for the presence of the mutant protein by inducing the synthesis of both soluble and membrane-associated lysosomal enzymes, and by internalizing lysosomal enzymes that were secreted by default. These data show that MPRs are limiting in the secretory pathway of cells expressing rab9 S21N and document the importance of MPR recycling and the rab9 GTPase for efficient lysosomal enzyme delivery.

Animals↗
PubMed1994

Anti-CD48 (murine CD2 ligand) mAbs suppress cell mediated immunity in vivo.

With the identification of murine CD48 as a homolog of the human CD2 ligand LFA-3 (CD58) and as a ligand itself for murine CD2, the anti-murine CD48 mAb HM48-1 was administered intravenously to investigate the role of CD48 in cell mediated immunity in vivo. Anti-CD48 mAb diminished the contact sensitivity response to the hapten trinitrophenol (TNP). mAb also inhibited in vivo priming for the subsequent generation of secondary, TNP-specific, cytotoxic T lymphocytes (CTL) in vitro. The inhibitory effect was most effective in the afferent or inductive phase of immunity for CTL, while anti-CD48 mAb was most inhibitory for the efferent or elicitative phase of contact sensitivity. Addition of anti-CD48 mAb directly to secondary CTL cultures also completely inhibited CTL generation, while addition to the lytic assay showed only minimal inhibition of CTL activity. Combining cells from mAb treated and untreated animals showed no evidence for suppressor cells. Further experiments revealed that mAb administered in vivo, as well as to culture, inhibited development of primary, alloantigen-specific CTL in vitro. Mixed lymphocyte reaction and phytohemagglutinin proliferation were partially suppressed by mAb administered in vivo or in vitro, whereas other mitogenic responses remained unaffected. Flow cytometric analysis revealed a moderate down modulation of CD48, CD3 and CD8 after treatment with anti-CD48. However, this did not represent T cell depletion since CD2, Thy-1.2 and Ig expression did not change. These results support a major unrecognized role for CD48 in diverse aspects of cell mediated immunity, affecting both CD4+ and CD8+ effector T cell function.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Gene transfer for transplantation. Prolongation of allograft survival with transforming growth factor-beta 1.

OBJECTIVE: The authors tested the ability of plasmid gene transfer to express transforming growth factor-beta 1 (TGF-beta 1), prolong allograft survival, and evaluate promoter effects on gene expression. SUMMARY BACKGROUND DATA: Delivery of immunosuppressants directly to allografts using gene transfer and gene therapy approaches may inhibit immune activation while avoiding the systemic toxicity of conventional immunosuppression. Candidate genes include soluble cytokines, which could be expressed at low levels throughout the graft while inducing a local immunosuppressive effect. Transforming growth factor-beta 1 is a soluble cytokine that has pleiotropic immunosuppressive effects. METHODS: Cardiac grafts from syngeneic (CBA/J, H-2k) or allogenic (C57BL/6, H-2b) donors were placed into CBA/J recipients. Purified plasmid DNA-encoding murine TGF-beta 1 or beta-galactosidase (Lac Z) under the control of RSV, SV40, MMTV, or pancreatic elastase promoters was injected into grafts at surgery. The Lac Z expression was determined by histologic examination and TGF-beta 1 expression by graft survival. Cytotoxic T lymphocyte and flow cytometric analyses were performed to evaluate the immunosuppressive effects of TGF-beta 1 in vitro. RESULTS: Plasmid DNA-encoding TGF-beta 1 prolonged survival from 12.6 +/- 1.1 days to 26.3 +/- 2.5 days (p < 0.02, Student's t test). The SV40 promoter was superior to the MMTV promoter in its ability to prolong survival. The effects of the plasmids were specific because Lac Z, antisense TGF-beta 1 inserts, or pancreatic elastase promoter did not prolong allograft survival. Histologic examination demonstrated Lac Z expression at least 14 days post-transplant in myocardial cells. Both RSV and SV40 promoters were effective in this respect, while a control null promoter was not. Toxicity testing showed that gene transfer of TGF-beta 1 did not alter survival or histology of syngeneic grafts. In addition, plasmids and purified TGF-beta 1 protein were not toxic to myoblasts in vitro. Recombinant TGF-beta 1 inhibited cytotoxic T lymphocyte generation and altered T cell surface receptor expression and subset expansion in vitro. CONCLUSION: Gene transfer/therapy with plasmid DNA encoding TGF-beta 1 in vivo achieves immunologic effects that prolong allograft survival. Multiple promoters effectively induce plasmid expression, which is achieved in cardiac myocytes for at least 2 weeks without toxicity or adverse systemic effects. Transforming growth factor-beta 1 inhibits immune responses by different mechanisms, revealed by in vitro analysis of T cell cytolytic function, subset distribution, and receptor display.

Animals↗
PubMed1994

Injecting drug use and HIV infection in southwest China.

OBJECTIVES: To determine the prevalence of drug injection among drug users, the seroprevalence of HIV and risk factors for HIV infection among injecting drug users (IDU), and to determine heterosexual transmission of HIV among IDU and their spouses in southwest China. METHODS: Using a cross-sectional design, we conducted an HIV seroprevalence and behavioral survey in three rural counties of Yunnan province, Ruili, Longchuan and Luxi in southwest China, bordering Myanmar (Burma). A total of 860 drug users were recruited in randomly selected communities at the three study sites (response rate, 97%). In addition, a random sample of 62 wives of HIV-infected IDU were assembled from 460 known HIV-positive IDU in Ruili and Longchuan (response rate, 81%). RESULTS: In the sample of 860 drug users, 33% reported injecting drugs. Among the 282 subjects who injected drugs, 82% began intravenous drug use after 1988; 64% injected drugs at least once every day. All subjects shared needles but none cleaned the injection equipment with alcohol or bleach. Overall, 49% tested HIV-positive. HIV seropositivity was independently correlated with a longer history of drug injecting, daily injecting, frequent needle-sharing, being younger, and living in Ruili county. Among the 62 wives of HIV-positive IDU, none used condoms during sex and 10% tested HIV-positive. CONCLUSIONS: We conclude that the introduction of HIV into drug-using communities and the rapid increase in heroin injecting in this population appear to have triggered an explosive HIV epidemic among IDU in southwest China. We recommend that AIDS prevention efforts should begin immediately and focus on discouraging the shift from opium smoking to heroin injecting, needle-sharing, and unprotected sex among drug users and their partners.

Adult↗
PubMed1994

High-sensitivity GafChromic film dosimetry for 125I seed.

The dose response of high-sensitivity GafChromic film to photons from 125I seeds for doses up to 200 Gy was established. The optical densities were measured using two types of densitometers: (a) a Macbeth spot densitometer with broadband light spectrum, and (b) an LKB He-Ne laser scanning microdensitometer with red light of wavelength 632.8 nm. The net optical density was found to be a power function of dose with exponents of 0.858 and 0.997, for the Macbeth and LKB densitometers, respectively. Film sensitivity with the LKB densitometer was about double of that with the Macbeth densitometer. The dose measurements were performed using the high-sensitivity GafChromic films for 125I model 6702 seed in solid water phantom. Each film was positioned parallel to the seed's long axis and centered at the seed's transverse axis. Films were exposed at various distances, ranging from contact to 3 cm from the seed center. The radiation dose delivered to the film center varied from 7 to 50 Gy, depending on the distance. The optical density at the film center was measured using both types of densitometers. Dose conversion was achieved with the established dose response curves for the respective densitometers. The dose values, along the seed's transverse axis obtained using both densitometers, were compared with each other, and also compared with published thermoluminescent dosimeter (TLD) data and Monte Carlo results. General agreement was found. It was concluded that the high-sensitivity GafChromic film measurement is a feasible method for 125I seed dosimetry in solid water phantom.(ABSTRACT TRUNCATED AT 250 WORDS)

Biophysical Phenomena↗
PubMed1994

Effects of GABA receptor blockage on the respiratory response to hypoxia in sedated newborn piglets.

Brain gamma-aminobutyric acid (GABA) levels increase during hypoxia, which may modulate the ventilatory response to hypoxia. To test the possibility that the depressed neonatal ventilatory response to hypoxia may be related to increased central nervous system GABA activity, 26 sedated spontaneously breathing newborn piglets (age 5 +/- 1 day, wt 1.7 +/- 0.4 kg) were studied. Minute ventilation (VE), oxygen consumption, heart rate, arterial blood pressure, and arterial blood gases were measured in room air and after 1, 5, and 10 min of hypoxia (inspired O2 fraction 0.10) before drug intervention. Immediately after these measurements, an infusion of saline or the GABA alpha-receptor blocker (bicuculline, 0.3 mg/kg iv) or beta-receptor blocker (CGP-35348, 100-300 mg/kg iv) was administered while animals were hypoxic. All measurements were repeated at 1, 5, and 10 min after initiation of the drug infusion. Basal VE was similar among groups. During hypoxia, VE increased significantly in the animals that received either a GABA alpha- or beta-receptor blocker but not in those receiving saline. Changes in arterial Po2, oxygen consumption, heart rate, and arterial blood pressure were similar among groups before and after saline or GABA antagonist infusion. These results suggest that the decrease in ventilation during the biphasic ventilatory response to hypoxia in the neonatal piglet is in part mediated through the depressant effect of GABA on the central nervous system.

Animals↗
PubMed1994

Impact of parallel heterogeneity on a continuum model of the pulmonary arterial tree.

Model arterial trees were constructed following rules consistent with morphometric data, Nj = (Dj/Da)-beta 1 and Lj = La(Dj/Da)beta 2, where Nj, Dj, and Lj are number, diameter, and length, respectively, of vessels in the jth level; Da and La are diameter and length, respectively, of the inlet artery, and -beta 1 and beta 2 are power law slopes relating vessel number and length, respectively, to vessel diameter. Simulated heterogeneous trees approximating these rules were constructed by assigning vessel diameters Dm = Da[2/(m + 1)]1/beta 1, such that m-1 vessels were larger than Dm (vessel length proportional to diameter). Vessels were connected, forming random bifurcating trees. Longitudinal intravascular pressure [P(Qcum)] with respect to cumulative vascular volume [Qcum] was computed for Poiseuille flow. Strahler-ordered tree morphometry yielded estimates of La, Da, beta 1, beta 2, and mean number ratio (B); B is defined by Nk + 1 = Bk, where k is total number of Strahler orders minus Strahler order number. The parameters were used in P(Qcum) = Pa [formula: see text] and the resulting P(Qcum) relationship was compared with that of the simulated tree, where Pa is total arterial pressure drop, Q is flow rate, Ra = (128 microLa)/(pi D4a (where mu is blood viscosity), and Qa (volume of inlet artery) = 1/4D2a pi La. Results indicate that the equation, originally developed for homogeneous trees (J. Appl. Physiol. 72: 2225-2237, 1992), provides a good approximation to the heterogeneous tree P(Qcum).

Algorithms↗
PubMed1994

Increased expression of luteinizing hormone/human chorionic gonadotropin receptor gene in human endometrial carcinomas.

Normal human endometrium expresses LH/hCG receptor gene. In the present study, we investigated whether human endometrial carcinomas also express this receptor gene. Reverse transcription-nested polymerase chain reaction amplified LH/hCG receptor sequences from human endometrial carcinoma just as it did those from normal human endometrium and human ovary as a positive control tissue. Northern blotting demonstrated that endometrial carcinomas contain a greater abundance of multiple LH/hCG receptor transcripts, which increased with increasing tumor grade. Western immunoblotting revealed that all grades of endometrial carcinomas contain multiple immunoreactive receptor proteins in greater abundance than normal endometrium. In situ hybridization and immunocytochemistry demonstrated not only the presence, but also higher LH/hCG receptor messenger ribonucleic acid and receptor protein levels in glands of endometrial carcinoma compared to glands in normal endometrium. Ligand blotting demonstrated that the 35-kilodalton protein receptor could bind [125I]hCG and that this binding was inhibited by excess unlabeled hCG. The binding was higher in endometrial carcinoma than in normal endometrium. Atrophic and endocervical glands from endometrial carcinoma samples contained very few or no receptors. In summary, our results demonstrate that human endometrial carcinomas not only contain but also appear to overexpress LH/hCG receptors compared to normal endometrium. This novel finding introduces previously unsuspected possibilities concerning the role of LH and its receptors in human endometrial carcinomas.

Adult↗
PubMed1994

Diagnostic pharmaco-scintigraphy with hepatic intra-arterial technetium-99m macroaggregated albumin in the determination of tumour to non-tumour uptake ratio in hepatocellular carcinoma.

Between October 1990 and March 1993, 124 patients who had hepatocellular carcinoma (HCC) underwent diagnostic pharmaco-scintigraphy with hepatic intraarterial technetium-99m macroaggregated albumin (TcMAA) to determine the tumourous to non-tumourous liver tissue uptake ratio (T/N ratio). There were 110 males and 14 females. Ages ranged from 16 to 73 with a median of 55 years. The range of T/N ratio was 0.7 to 19.3 with a median of 3.8. 12 patients with inoperable HCC were subsequently selected by predetermined criteria to undergo treatment with hepatic intraarterial yttrium-90 microspheres and the T/N ratios in these patients were validated by beta probe dosimetry and liquid scintillation count of multiple liver biopsies. The T/N ratio determined by preoperative diagnostic TcMAA scan correlated well with intraoperative beta probe dosimetry, with coefficient of correlation r = 0.82. Preoperative TcMAA scan also correlated well with liquid scintillation count of biopsy specimens, with r = 0.96. We conclude that TcMAA scan can be used to determine the T/N ratio in patients with HCC, thus allowing better selection of patients with inoperable tumours for loco-regional therapy.

Adolescent↗
PubMed1994

Selective internal radiation therapy with intra-arterial iodine-131-Lipiodol in inoperable hepatocellular carcinoma.

UNLABELLED: From August 1990 to June 1993, 26 patients with inoperable hepatocellular carcinoma were treated with intra-arterial iodine-131-Lipiodol (131I-L). METHODS: Iodine-131-Lipiodol was given through either an implantable arterial port (9 patients) or during hepatic angiography (17 patients). All 26 patients had multiple lesions, 3 had involved resection margin after surgical resection and 1 had diffuse infiltrative lesions. The median size of the largest tumor among 22 patients with a measurable lesion was 4.5 cm (2-9.5 cm). The end points are tumor response in terms of tumor size, change in serum alpha-fetoprotein level, toxicity of treatment and overall survival. RESULTS: Twenty-three patients received a single treatment of 1.11-2.22 GBq (30-60 mCi)131I-L. Three patients received 2.22-4.44 GBq (60-120 mCi)131I-L in three fractions. Considering both radiological regression and reduction in serum alpha-fetoprotein level as objective response criteria, the overall response rate was 52% (13 out of 25 patients with evaluable disease). Ten out of 15 patients who had raised alpha-fetoprotein levels had more than 50% reduction and 8 patients had more than 90% reduction in alpha-fetoprotein level. Since analysis, 19 patients have died and 7 remain alive, giving a minimum median survival of 6 mo (range 1.2-16.6 mo), with 4 surviving more than 1 yr calculated from the day of treatment. There was only one patient who had late deterioration of liver function compatible with radiation hepatitis. There was no bone marrow toxicity documented in any patients. CONCLUSION: Treatment with intra-arterial 131I-L was well tolerated in patients with inoperable hepatocellular carcinoma and produced an objective response of 52% with median survival of 6 mo. A fractionated dose of 131I-L was feasible and the radiation dose could be escalated safely.

Carcinoma, Hepatocellular↗
PubMed1994

[MBP P89-101 induced experimental allergic encephalomyelitis in mice and establishment of CD4+ T cell line specific to MBP P89-101].

SJL/J mice were immunized with peptide 89-101 of myelin basic protein in FCA and developed EAE around 13th day after immunization. Lymph-nodes were collected at the time of onset and lymphocytes were prepared and cultured with MBP P89-101 in vitro for 3 weeks. X-ray irradiated (3000R) syngeneic spleen cells were added as antigen presenting cells. Antigen stimulated blast cells were isolated with Ficoll-Hypaque. MBP P89-101 specificity of cells were measured by 3H-TdR incorporation. MBP P89-101 activated cells were stained with PE-CD4 and analyzed by FACS. The results showed that all of the blast cells were of CD4 positive phenotype, specific to MBP P89-101.

Animals↗
PubMed1994

Viremia and serological responses in adult chickens infected with western equine encephalomyelitis and St. Louis encephalitis viruses.

Adult hens, similar to those used for arbovirus surveillance, were experimentally infected with western equine encephalomyelitis (WEE) and St. Louis encephalitis (SLE) viruses to describe the viremia response, to compare serological testing methods, and to evaluate a new method of collecting whole blood onto filter paper strips from lancet pricks of the chicken comb. Young (19 weeks), but not old (38 weeks), hens developed a low-titer, transient viremia for a 1-day period. Immunoglobulin G (IgG) was detected by days 10 and 14 after infection with WEE and SLE viruses, respectively, by indirect fluorescent antibody tests, hemagglutination inhibition tests, and plaque reduction neutralization tests on sera and in direct enzyme immunoassays (EIA) on both sera and eluates from filter paper samples. Immunoglobulin M (IgM) was first detected in sera 2 and 3 days before IgG, respectively, but IgM could not be detected reliably in eluates from dried blood. Sera and dried blood samples collected from naturally infected sentinel chickens gave comparable results when tested by an EIA for IgG.

Animals↗