Biomedical subjects

G Lin

Publications and source records attributed to G Lin.

At least 163 records · Page 9Linked to original sources

PubMed1994

Expression and characterization of cM-T413, a chimeric anti-CD4 antibody with in vitro immunosuppressive activity.

Anti-CD4 monoclonal antibodies (mAbs) have shown considerable promise in the treatment of rheumatoid arthritis, psoriasis, and allograft rejection and may have potential use in blocking HIV-1 infection. One such anti-CD4 mAb we have developed, chimeric M-T412 (or cM-T412), has been used in clinical trials to treat rheumatoid arthritis, generalized postular psoriasis, and other autoimmune diseases. Here we report the cloning and expression of a second chimeric anti-CD4 mAb using M-T413, a murine mAb that blocks HIV-1 infection of H9 cells. We cloned the immunoglobulin light and heavy chain variable regions of M-T413, combined them with the human kappa (light chain) or G1, G2, G3 and G4 (heavy chain) constant regions in human expression vectors, and expressed these chimeric mAbs in 653 cells. Like chimeric M-T412 IgG1, the chimeric M-T413 mAbs inhibit T-cell proliferation in the mixed lymphocyte response and thus can act to immunosuppress CD4+ T-cell response. In contrast to M-T412, however, the M-T413 chimeric mAbs have reduced activity in an antibody-dependent cell-mediated cytotoxicity (ADCC) assay using human CD4+ target and effector cells. We conclude that the chimeric M-T413 mAbs have potential utility in treating autoimmune disease and may be useful as prophylactics in preventing HIV-1 infection.

Animals↗

PubMed1994

Oligohydramnios: maternal complications and fetal outcome in 145 cases.

One hundred and forty-five cases of oligohydramnios in the second and third trimester were diagnosed by ultrasonography out of 25,000 obstetrics patients (0.58%). In this group, pregnancy complications included hypertension (22.1%) and bleeding in the second trimester (4.1%). We found a high incidence of meconium-stained amniotic fluid (29.1%), fetal distress (7.9%) and premature placental separation (4.2%). IUGR occurred in 24.5% of cases. Asphyxia during labor occurred in 11.5% and different other perinatal problems in 23.5%. Cesarean section was performed in 35.2% of these pregnancies. Seventeen percent of the cases presented as breech. Intrauterine fetal death occurred in 5.5% of these pregnancies. The gross perinatal mortality was 16% and the corrected perinatal mortality was 10.7%. The overall rate of fetal malformations was 11% and that of lethal malformations 4.8%. The skeletal (7.6%) and urinary system (4.1%) were the predominant systems affected. Oligohydramnios is associated with a higher rate of pregnancy complications and increased fetal morbidity and mortality, and thus termination should be considered when pulmonary maturity is present or in cases of fetal distress.

Abortion, Spontaneous↗

PubMed1993

An experimental study and clinical pilot trials on yttrium-90 glass microspheres through the hepatic artery for treatment of primary liver cancer.

BACKGROUND: Yttrium-90 (90-Y) glass microsphere is a new kind of radiation microsphere for internal radiation therapy of primary liver cancer (PLC). The study was carried out by administration of 35 microns nondegradable 90-Y glass microsphere through the hepatic artery for treatment of PLC. METHODS: Six rabbits were injected with 185-1480 megabecquerels (MBq) of 90-Y glass microspheres, and three rabbits were injected with 35-300 mg of 89-Y glass microspheres for the toxic test. Eighteen patients received 2442-5550 MBq of 90-Y glass microspheres for the treatment of PLC. Whole blood counts, liver function, and imaging examination were performed. Pathologic examinations were performed on all rabbits. RESULTS: All rabbits were apparently well after absorbing 114.1-845.2 Gy 90-Y glass microspheres in the liver but showed transient degeneration of hepatocytes and portal fibrosis histologically. The mean absorbed dose in liver tissue of patients with PLC was 30.33 Gy, whereas that in tumor tissue was 88 Gy and the highest in tumor tissue, 186.36 Gy. The mean tumor:liver tissue ratio was 3:1; the highest, 14:1. Fourteen patients were still alive after half a year's follow-up and 6 of these 14 were still alive after 1 year. CONCLUSIONS: The rabbits could tolerate up to eight-fold of the upper limit of clinical dose (100 Gy). Good responses to the radiation therapy of 90-Y glass microspheres in patients with localized and hypervascular or vascular mass were achieved. Contraindications for the therapy were presence of massive hepatic arterioportal shunt and cancer emboli in the main portal vein. It is safe and applicable to deliver 90-Y glass microspheres in large doses through the hepatic artery for internal radiation treatment of PLC.

Adult↗

PubMed1993

Cloning, sequencing and regulation of an mRNA encoding porcine interleukin-1 beta.

Interleukin 1 (IL-1) is a cytokine that mediates a variety of immunological responses. We report here the isolation of a porcine IL-1 beta cDNA from an alveolar macrophage library. The complete cDNA sequence is 1458 bp in length and has an open reading frame of 803 bp, encoding a 267-amino-acid (aa) protein with an approximate molecular size of 31 kDa. The porcine IL-1 beta cDNA sequence shows homologies of 82.0, 81.0, 74.0, and 74.0% with the bovine, sheep, human, and murine sequences in the protein coding regions, respectively. Northern blot analysis reveals a single 1.7-kb mRNA species that is differentially regulated by lipopolysaccharide, phorbol myristate acetate, and tumor necrosis factor but is not regulated by human recombinant IL-1. Porcine IL-1 beta is down-regulated by dexamethasone, polymyxin B, and IL-4 in a fashion kinetically similar to the other reported species.

Amino Acid Sequence↗

PubMed1993

The 0.25-nm X-ray structure of the Bowman-Birk-type inhibitor from mung bean in ternary complex with porcine trypsin.

The structure of the Bowman-Birk-type inhibitor from mung bean Phaseolus aureus has been determined in ternary complex with porcine trypsin. The complex formed crystals of the trigonal space group P3(1)21 which diffracted to a resolution of 250 pm. Each of the two mung bean protease reactive sites is bound to trypsin according to the standard mechanism for serine proteinase inhibition. The binding loops thereby adopt the canonical conformation for the standard mechanism; however, the sub-van der Waals contact between the active-site serine O gamma (195) and the P1 carbonyl carbon of both loops is significantly smaller (210 pm) than hitherto observed, with continuous electron density connecting the two atoms. The inhibitor is formed by two double-stranded antiparallel beta-sheets, which are connected into a moderately twisted beta-sheet by a network of hydrogen bonds involving main-chain atoms and two water molecules. All contacts with neighbors in the crystal lattice occur between trypsin molecules. This apparently gives rise to an unusual form of disorder where the complexes pack in two orientations Ta:MaMb:Tb and Tb:MbMa:Ta (Ta, Tb = trypsin, Ma = mung bean loop I, Mb = mung bean loop II), such that the asymmetric unit consists of the ternary complex in two orientations, each with half occupancy. This is nearly equivalent to an asymmetric unit which has one trypsin molecule with full occupancy and one mung bean inhibitor with half occupancy and a crystallographic twofold symmetry axis through its center. Because of the approximate twofold symmetry of the inhibitor itself, however, the electron density was interpretable for most of the inhibitor (17 residues at the termini were not resolved) and shows evidence of its double orientation.

Animals↗

PubMed1993

Synthesis of the N-oxides of phenothiazine antipsychotic agents.

Chlorpromazine N-oxide, fluphenazine N4'-oxide, prochlorperazine N4'-oxide, sulforidazine N-oxide, and trifluoperazine N4'-oxide were synthesized by oxidation of the designated nitrogen atom in the N-10 side chain of the respective parent drug with 3-chloroperoxybenzoic acid. In the case of trifluoperazine, a stepwise increase in the amount of oxidant yielded the N1',N4'-dioxide and N1',N4',S-trioxide. The N',S-dioxides of chlorpromazine and sulforidazine were obtained by hydrogen peroxide oxidation of the appropriate parent drug.

Antipsychotic Agents↗

PubMed1993

Enhanced detection of intracellular organism of swine proliferative enteritis, ileal symbiont intracellularis, in feces by polymerase chain reaction.

A sensitive assay based on amplification of a 319-bp DNA fragment of the intracellular bacterium of swine proliferative enteritis was developed for the detection of the organism in the feces of swine. A vernacular name, ileal symbiont intracellularis (IS-intracellularis), has recently been published for the intracellular bacterium, which was formerly known as a Campylobacter-like organism (C.J. Gebhart, S.M. Barnes, S. McOrist, G.F. Lin, and G.H.K. Larson, Int. J. Syst. Bacteriol. 43:533-538, 1993). As few as 10(1) IS-intracellularis organisms purified from intestinal mucosa, or 10(3) IS-intracellularis per g of feces, were detected. No amplification product was produced from a polymerase chain reaction performed on DNA extracted from the feces of healthy pigs. A 319-bp DNA fragment specific for IS-intracellularis was produced on amplification of DNA from the feces of pigs with experimental and naturally occurring proliferative enteritis.

Animals↗

PubMed1993

The metabolism of piperidine-type phenothiazine antipsychotic agents. II. Sulforidazine in dog and human.

1. The metabolism of sulforidazine was studied in female dogs and adult male humans after oral administration of 37.5 mg and 25.0 mg, respectively. 2. Metabolites in organic extracts of dog urine were separated by h.p.l.c. and individually collected prior to mass spectrometric analysis, while organic extracts of human urine were directly subjected to plasmaspray h.p.l.c.-mass spectrometric determination. In the case of phenolic metabolites, the urinary extracts from both species were derivatized with a silylating reagent (with or without prior enzymic hydrolysis) and subsequently analysed by h.p.l.c.-mass spectrometry. The structures of metabolites with the exception of phenols were confirmed by comparison of their mass spectra and chromatographic behaviours with those of authentic standards. 3. The compounds identified in urine of both species were sulforidazine, two diastereomers of sulforidazine ring sulphoxide, the lactam of sulforidazine ring sulphoxide and a phenolic derivative of sulforidazine, whereas sulforidazine N-oxide and the lactam of sulforidazine were identified only in human urine. Moreover the phenolic metabolite was present in human urine in both unconjugated and conjugated forms, whereas dog urine had only the conjugated form. 4. Sulforidazine and some of its major metabolites were quantified by an h.p.l.c. method. The mean urinary excretions (0-48 h) of sulforidazine were similar in human (n = 3) and dog (n = 3) (5.9 +/- 0.7% and 7.2 +/- 1.9%), as were the excretions of sulforidazine ring sulphoxide (13.2 +/- 4.6% and 13.3 +/- 4.4%), while the lactam of sulforidazine ring sulphoxide was a major metabolite only in human (7.5 +/- 2.8% and < 0.1%). The lactam of sulforidazine was a minor metabolite in human. 5. The metabolites observed in human urine were similar to those previously reported in rat, except that sulforidazine N-oxide was found only in human, whereas the two diastereomers of N-desmethylsulforidazine ring sulphoxide were observed only in rat. These data suggest that rat may be a more suitable animal than dog for further study of the metabolism of the piperidine ring of sulforidazine.

Adult↗

PubMed1993

The metabolism of piperidine-type phenothiazine antipsychotic agents. III. Mesoridazine in dog, human and rat.

1. The metabolism of mesoridazine was studied in female rats (20 mg/kg, oral), female dogs (50 mg over 30 h, oral) and adult male volunteers (25 mg, oral). 2. Solvent extracts of urines from each species were directly analysed by h.p.l.c.-mass spectrometry with a plasmaspray interface. In the case of phenolic metabolites the urinary extracts were derivatized with a silylating reagent (with and without prior enzymic hydrolysis) prior to analysis. The structures of metabolites, with the exceptions of mesoridazine N-oxide and phenols, were confirmed by comparison of their chromatographic behaviours and mass spectra with those of authentic standards. 3. Compounds identified in the urine of all three species were mesoridazine, sulforidazine, mesoridazine ring sulphoxide, sulforidazine ring sulphoxide, N-desmethylmesoridazine ring sulphoxide, the lactam of sulforidazine ring sulphoxide and phenolic derivatives of mesoridazine and sulforidazine. Whereas the unconjugated phenolic metabolite of sulforidazine was present in urine of all three species, the conjugated form was identified only in dog and rat urines. Also, the unconjugated phenolic metabolite of mesoridazine was identified only in the urine of dog and human, but rat urine contained only the conjugated form. 4. Other metabolites found were: the lactam of mesoridazine (rat), the lactam of mesoridazine ring sulphoxide (rat and human), mesoridazine N-oxide (human) and sulforidazine N-oxide (dog and human). 5. Mesoridazine and six of its metabolites present in urines of human, rat and dog were quantified by a h.p.l.c.-u.v. method. The mean total excretion of measured analytes in human, rat and dog were 6.3, 2.6 and 29.1%, respectively. The excretion of the lactam of sulforidazine ring sulphoxide was greater in human (0.4%) and rat (0.2%) than dog (0.02%). Moreover, the urinary excretion of the lactam of mesoridazine ring sulphoxide in human and rat constituted 0.4% and 0.2%, respectively. Of the three lactams found in rat the lactam of mesoridazine was present in the least amount (0.05%). 6. Interspecies comparison of the lactam metabolites indicated that both qualitatively and quantitatively human more closely resembled rat than dog. On the other hand, N-oxide metabolites were detected in human and dog but not in rat.

Adult↗

PubMed1993

Metabolism of piperidine-type phenothiazine antipsychotic agents. IV. Thioridazine in dog, man and rat.

1. The metabolism of thioridazine was studied in adult male volunteers, female rat and female dog after oral administration of 50 mg, 20 mg/kg and 100 mg over 30 h, respectively. 2. Metabolites in organic extracts of the urine obtained from each species were analysed by plasmaspray h.p.l.c.-mass spectrometry. For phenolic metabolites the crude extracts from each species were derivatized with a silylating reagent (with and without prior enzymic hydrolysis) prior to h.p.l.c.-mass spectrometric analysis. The structures of metabolites, with the exception of phenols, were confirmed by comparison of their chromatographic behaviours and mass spectral data with those of authentic standards. 3. The metabolites identified in the urine of all three species were mesoridazine, sulforidazine, thioridazine ring sulphoxide, mesoridazine ring sulphoxide, sulforidazine ring sulphoxide, the lactam of mesoridazine ring sulphoxide and unconjugated phenolic derivatives of mesoridazine and sulforidazine. Other compounds observed were: unchanged thioridazine (dog, rat), sulforidazine N-oxide (man), N-desmethylthioridazine ring sulphoxide (dog, rat), N-desmethylmesoridazine ring sulphoxide (dog, rat), the lactam of sulforidazine ring sulphoxide (rat, man), phenolic derivative of thioridazine in unconjugated form (rat), and conjugated form (man), and conjugated phenolic derivative of mesoridazine (man). 4. Thioridazine and six of its metabolites present in the urine of man, rat and dog were quantified by a h.p.l.c.-UV procedure. The mean total urinary excretion (+/- SD) of the measured analytes in man, rat and dog were determined to be 4.3 +/- 2.9, 4.8 +/- 1.7 and 12.1 +/- 5.4% of the dose, respectively. The mean excretion of the lactam of mesoridazine ring sulphoxide was greater in man (1.2 +/- 1.0%) and rat (0.2 +/- 0.2%) than dog (< 0.02%). Moreover, the mean excretion of the lactam of sulforidazine ring sulphoxide was quantifiable in both man (0.5 +/- 0.4%) and rat (0.2 +/- 0.2%). 5. Interspecies comparison of the lactam metabolites indicated that both qualitatively and quantitatively, man more closely resembled rat than dog. Similar observations were previously reported for mesoridazine and sulforidazine, therefore rat may be a more suitable animal than dog to undertake further study of the importance of C-oxidation of the piperidine ring of this class of drug.

Adult↗

PubMed1993

Molecular characterization of alpha 2-adrenergic receptors regulating intestinal electrolyte transport.

Norepinephrine (NE) is an important neuromodulator of active Na+ and Cl- transport by the small intestine; however, the cellular targets and the adrenergic receptor (AR) subtype mediating its effects on ion transport have not been clearly defined. NE inhibited short-circuit current in submucosal-mucosal sheets of porcine distal jejunum under basal conditions and after electrical transmural stimulation of intrinsic neurons. A membrane fraction (P2) prepared from the submucosa of porcine jejunum was enriched in specific [3H]saxitoxin binding sites, relative to other submucosal fractions. This fraction contained homogeneous and high affinity sites binding the alpha 2-AR antagonist [3H]yohimbine (Kd = 0.39 +/- 0.03 nM). A prazosin versus oxymetazoline Ki ratio of 218 was obtained for the submucosal AR binding site, suggesting that it represents a neuronal alpha 2A-AR. A cell membrane fraction prepared from the mucosa exhibited specific and saturable high affinity binding of the muscarinic cholinergic antagonist [3H] quinuclidinyl benzilate (Kd = 77 +/- 9 pM) but displayed minimal specific binding of [3H]saxitoxin or [3H]yohimbine. A [32P]cDNA probe derived from the human alpha 2-C10 gene encoding the alpha 2A-AR hybridized to a 3.8-kilobase message that was prevalent in poly(A)+ RNA isolated from the jejuno-ileal submucosa and was also detected in porcine cerebral cortex and kidney; no message was detected in RNA isolated from the jejunal mucosa. These results suggest that NE modulates active ion transport in the small intestine through interactions with a submucosal alpha 2A-AR probably associated with enteric neurons.

Animals↗

PubMed1993

Yttrium-90 glass microspheres injected via the portal vein. An experimental study.

Nondegradable glass microspheres (35 mu) were injected into the portal vein for toxicity test in 15 rabbits. In 10 animals the microspheres were loaded with 90Y, giving liver absorbed doses between 24.6 and 437.4 Gy, and in 5 with 89Y (control group). The total amount of microspheres injected in each animal varied between 35 and 140 mg. The rabbits in the experimental group tolerated the effect of radioembolization in a dose 4 times higher than the upper limit of the clinical dose (100 Gy). After injection of 90Y glass microspheres into the portal vein of rats with diethylnitrosamine (DEN)-induced hepatic carcinoma, the microspheres, in addition to the liver parenchyma, accumulated in central and peripheral parts of the cancer nodules, causing necrosis. The internal radiation therapy of 90Y glass microspheres delivered via the portal vein may be an effective nonsurgical method for the treatment of liver cancer, especially in small nodules.

Animals↗

PubMed1992

Proficiency of the Tradescantia-micronucleus image analysis system for scoring micronucleus frequencies and data analysis.

The Tradescantia-micronucleus (Trad-MCN) bioassay is an efficient short-term test for genotoxicity of pollutants. In order to increase the efficiency and to standardize the micronucleus (MCN) scoring process, an automated scoring system was developed using the principle of image analysis in computer science. This assemblage is called the Tradescantia-micronucleus image analysis (Trad-MCNIA) system. The MCN frequencies scored by this system were compared with those scored by human observation for its proficiency. A set of low MCN frequency (around 5 MCN/100 tetrads) slides prepared from a control group, a set of medium MCN frequency (around 20 MCN/100 tetrads) slides prepared from sodium azide treated plant cuttings and a set of high MCN frequency (around 50 MCN/100 tetrads) slides prepared from X-ray treated materials were used for this study. In the low MCN frequency slides, the Trad-MCNIA system scored about the same value as human observation. In the medium and high frequency slides, MCN frequencies scored by the system were lower than those scored by human observers. This discrepancy was corrected by increasing the power of the objective of the microscope in the system. The MCN frequencies scored by the system attained 90% congruity with those scored by human observers after the correction. The scoring speed of the system was about 3.5 times as fast as that by human observers, and the data could be statistically analyzed immediately after the data scores were recorded. Further improvements can be made by upgrading the video camera and the computer speed.

Azides↗

PubMed1992

Stimulation of thymidine kinase activity in baculovirus infected cells is not due to a virus-coded enzyme.

A polyhedrin-positive recombinant autographa californica nuclear polyhedrosis virus (AcNPV) carrying a herpes simplex virus thymidine kinase gene under the control of the SynXIV promoter, a fusion of synthetic and linker-modified polyhedrin promoters, has been constructed. When this recombinant baculovirus was used to infect a variant of Spodoptera frugiperda cells deficient in thymidine kinase (TK-), a high level of TK activity was detected. These results, in conjunction with the demonstration that AcNPV could replicate in TK- S. frugiperda cells and no TK activity was found throughout infection, imply that the wild type virus-stimulated TK activity observed in S. frugiperda (TK+) cells is not contributed by a virus-coded enzyme.

Animals↗

PubMed1992

The metabolism of piperidine-type phenothiazine antipsychotic agents. I. Sulforidazine in the rat.

1. The metabolism of the piperidine-type, phenothiazine antipsychotic agent, sulforidazine, was studied in female rats after a 20 mg/kg single oral dose. 2. Compounds identified in urine were sulforidazine, sulforidazine ring sulphoxide, the lactam of sulforidazine, the lactam of sulforidazine ring sulphoxide, two diastereomers of N-desmethylsulforidazine ring sulphoxide and a phenolic derivative of sulforidazine. 3. Metabolites were separated by h.p.l.c. prior to mass spectrometric or g.l.c.-mass spectrometric analysis. Except in the case of the phenolic metabolite, structures were confirmed by direct comparison of electron impact mass spectra and chromatographic behaviour with those of authentic samples. To facilitate identification of the phenolic metabolite the crude urinary extract was treated with a silylating reagent and analysed by h.p.l.c.-mass spectrometry with a plasmaspray interface. 4. Despite the availability of authentic standards of sulforidazine N-oxide and sulforidazine N,S-dioxide neither of these compounds could be identified in urinary extracts obtained from rats. 5. Sulforidazine underwent extensive metabolism in rats as only 2.3 +/- 0.4% (n = 5) of the dose was present as unchanged sulforidazine in 24 h urine. The lactam of sulforidazine (0.1 +/- 0.1%) was a minor metabolite whereas the lactam of sulforidazine ring sulphoxide was 3.2 +/- 2.6% dose. 6. Sulforidazine sulphoxide (12.1 +/- 1.6%) was a major metabolite and its diastereomers were present in similar amounts.

Animals↗

PubMed1992

The establishment of rat-mouse hybridomas secreting anti-aflatoxin M1 antibodies and the properties of their monoclonal antibodies.

After a comparison of anti-AFM1-BSA antibody responses between rat and mouse, the spleen cells of rat with stronger responses were chosen as parent cells for fusing with mouse myeloma cells P3X63-Ag8.653. Through HAT medium selection, RIA screening and cloning, five well growing rat-mouse hybridoma clones were obtained that could secret anti-AFM1 antibodies stably. The results from ELISA and competitive binding RIA further proved that the 5 McAbs are direct against AFM1, with significant cross reaction to its derivative, AFB1. The average affinity constant of the 5 McAbs is 10(9)-10(11) l/M. It signifies that these monoclonals have potential application value for the construction of AF detection kit.

Aflatoxin M1↗

PubMed1992

[A new method of enveloping volatile oils in Chinese medicinal herbs with beta-cyclodextrin].

A comparison has been made of the enveloping rate of volatile oil by three different methods with beta-cyclodextrin. The result indicates that the saturated water solution enveloping method is very close to the gas-liquid enveloping method, P greater than 0.05, but the liquid-liquid enveloping method is apparently higher than the saturated water solution enveloping method, P less than 0.01.

Cyclodextrins↗

PubMed1991

Multiple organ failure (MOF) after intestinal operations--a clinical and statistical study of the past 5 years.

Multiple Organ Failure that occurred in 35 cases out of a total of 1498 cases after intestinal surgery were studied by an analysis of the clinical and statistical data from the past 5 years (1984-1988). 1. The incidence of MOF after intestinal surgery was 2.3%. 2. Twenty-eight of MOF resulted from severe infections. 3. The incidence of infection was highest after esophageal operations. 4. Hepatic failure was the most common type of primary organ failure and renal failure was the second most common. 5. The prognosis for MOF was very poor with a survival rate of 8.7%.

Digestive System Surgical Procedures↗