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Biomedical subjects

S Lu

Publications and source records attributed to S Lu.

At least 343 records · Page 19Linked to original sources

Interleukin 12 at the site of disease in tuberculosis.

Interleukin 12 (IL-12), a heterodimeric cytokine composed of p40 and p35 chains, has potent immunologic effects in vitro. We used tuberculous pleuritis as a model to study the immunoregulatory potential of IL-12 in vivo at the site of human infectious disease. Messenger RNAs for p40 and p35 were detected in pleural fluid from six of six patients by reverse-transcription polymerase chain reaction. By using an ELISA that detected both free p40 and heterodimeric IL-12, we found that mean concentrations were 585 +/- 89 pg/ml in pleural fluid of patients with tuberculous pleuritis, which were significantly higher than those in serum of the same patients (54 +/- 36 pg/ml), or in malignant pleural effusions (123 +/- 35 pg/ml). By using an ELISA specific for heterodimeric IL-12, we found that mean concentrations in pleural fluid of patients with tuberculous pleuritis were 165 +/- 28 pg/ml and undetectable in serum of the same patients, or in malignant pleural effusions. Bioactive IL-12 was detectable in five of five supernatants of pleural fluid cells stimulated with Mycobacterium tuberculosis. Addition of anti-IL-12 antibodies suppressed proliferative responses of pleural fluid cells to M. tuberculosis by 36 +/- 7%. These data indicate that IL-12 may play a role in the human immune response to infectious agents in vivo. We hypothesize that IL-12 contributes to the antimycobacterial immune response by enhancing production of interferon-gamma, facilitating development of Th1 cells and augmenting cytotoxicity of antigen-specific T cells and natural killer cells.

Base Sequence↗

Expression cloning of a rat hepatic reduced glutathione transporter with canalicular characteristics.

Using the Xenopus oocyte expression system, we have previously identified an approximately 4-kb fraction of mRNA from rat liver that expresses sulfobromophthalein-glutathione (BSP-GSH)-insensitive reduced glutathione (GSH) transport (Fernandez-Checa, J., J. R. Yi, C. Garcia-Ruiz, Z. Knezic, S. Tahara, and N. Kaplowitz. 1993. J. Biol. Chem. 268:2324-2328). Starting with a cDNA library constructed from this fraction, we have now isolated a single clone that expresses GSH transporter activity. The cDNA for the rat canalicular GSH transporter (RcGshT) is 4.05 kb with an open reading frame of 2,505 nucleotides encoding for a polypeptide of 835 amino acids (95,785 daltons). No identifiable homologies were found in searching various databases. An approximately 96-kD protein is generated in in vitro translation of cRNA for RcGshT. Northern blot analysis reveals a single 4-kb transcript in liver, kidney, intestine, lung, and brain. The abundance of mRNA for RcGshT in rat liver increased 3, 6, and 12 h after a single dose of phenobarbital. Insensitivity to BSP-GSH and induction by phenobarbital, unique characteristics of canalicular GSH secretion, suggest that RcGshT encodes for the canalicular GSH transporter.

Amino Acid Sequence↗

[Studies on Clonorchiasis sinensis control in Sanshui City, Guangdong province].

During 1986 to 1988 and 1990 to 1992, Dongyong Township and Guanyuan Township in Sanshui City, Guangdong Province were selected as demonstration areas for clonorchiasis sinensis control by using measures of repeated examination and treatment respectively. After two years' examination and treatment, the population infection rates were from 43.6% to 13.2% in Dongyong Township and from 78.5% to 36.3% in Guanyuan Township. The first intermediate host was Alocimma longicornis, and the second intermediate hosts were Parabramis bransula and Ctenopharyngodon idellus. The adult worms of Clonorchis sinensis were found in the bile ducts of cats, dogs and pigs which may be the reservoir hosts.

China↗

[Carotid body tumor: diagnosis and surgical treatment].

Carotid body tumors are rarely encountered and can present a difficult surgical problem. During the period of June 1988 to November 1992, 8 patients were operated on for carotid body tumors at PLA General Hospital. Details of the surgery, morbidity and outcome of these patients are presented. Our experience suggests that: 1) The presence of a pulsatile neck mass located in the region of carotid triangle, vertically fixed and laterally mobile, should raise the suspicion of a carotid body tumor; 2) Color Doppler flow imaging has a role to play in the diagnosis of carotid body tumor; 3) DSA is very important for a number of reasons, especially for the use of concomitant embolization; 4) Management of these tumours is primarily surgical; 5) The decision whether to resect the carotid artery or not can only be made intra-operatively based on status of the patient and tumor, there might be 4 surgical options open to the operators.

Adult↗

[Restrictive fragment length polymorphism analysis of gamma-crystallin in congenital cataract families].

Using gamma-crystallin gene probe P5G1, we investigated the RFLP in two large families of congenital cataracts and normal people, calculated the allelic gene frequency and defined the haplotypes by genetic linkage analysis. In accordance with foreign reports, TaqI/p5G1 detected 3 polymorphic sites, and the allelic gene frequency was close to that in foreign reports. However, foreign reports claimed that the haplotype P was linked to Coppock cataracts, but we did not find such linkage by haplotype analysis. The result suggests that not all the inherited cataracts are linked to gamma-crystallin gene, and the haplotype P should not be simply regarded as genetic marker in prenatal diagnosis.

Cataract↗

Guardianship networks for rural psychiatric patients. A non-professional support system in Jinshan County, Shanghai.

This paper describes the 'rural guardianship network' method of managing persons with severe mental illnesses and reports on a retrospective case-control study that compares the outcome of 561 schizophrenic patients from townships with guardianship networks to that of 103 schizophrenic patients from a township without guardianship networks. Each patient enrolled in a guardianship network is assigned a guardian--usually a family member--who ensures that the patient takes medication and gets medical follow-up, and reports any changes in the patient's condition to the village health worker or the township doctor who is responsible for psychiatric care. These guardians are supported and supervised by management groups at the village and township levels composed of government officials, medical administrators, physicians from township hospitals, and village health workers. Compared with patients who are not enrolled in guardianship networks, enrolled patients have significantly lower rates of hospital admission, lower rates of socially disruptive behaviour, and lower levels of psychopathological symptoms. The rural guardianship network is an effective and economical means of providing close supervision of mentally ill patients in their homes.

Adolescent↗

[Effect of arginine on lymphocyte responses to ConA in burned mice].

It is well accepted that nutritional support improves the immunologic functions in burned patients. Arginine has been demonstrated to have tissue-specific properties which induce beneficial effects upon the immune system. A series of experiments are carried out, in order to evaluate the immune effect of arginine on burned mice. 1. Lymphocytes from both burned and unburned mice are harvested and incubated in various concentrations of arginine solution for 72 hours, and ConA-stimulating lymphocyte transformation is determined after incubation. 2. Burned animals are divided into four groups. Standard diets for nutritional support are formulated. These formulas contain an identical carbohydrate and lipid (61% and 15% of total energy respectively) intake with varied proportions of protein for each group (24%, 23%, 22%, and 20% of total energy, respectively), in addition. 0%, 1%, 2% and 4% of protein energy is supplied by arginine for different groups. Lymphocyte proliferations in responses to ConA stimulation are determined on the 7th postburn day. The data shows that, in vitro study, increasing arginine concentrations enhanced lymphocyte responses to ConA. The arginine needed level for optimal lymphocyte responses is 1.8 mmol/L in burned mice and 0.9 mmol/L in unburned controls. This difference indicates that in burned mice, a higher arginine concentration is required for better lymphocyte responses. On the contrary, further increase of arginine concentration do not give better response. When varied amounts of arginine are given in the diet to the burned mice, the degree of lymphocyte response to ConA is different. The amount of arginine which supplies 2% of total energy is found to be optimal.

Animals↗

Patterns of cytokine production by mycobacterium-reactive human T-cell clones.

To gain insight into the functional capacity of human T cells in the immune response against Mycobacterium tuberculosis, we evaluated the spectrum of cytokines produced by mycobacterium-reactive human T-cell clones. Nine of 11 T-cell clones bearing alpha beta or gamma delta T-cell receptors produced both Th1 and Th2 cytokines, a pattern resembling that of murine Th0 clones. The most frequent pattern was secretion of gamma interferon, tumor necrosis factor alpha (TNF), and interleukin-10 (IL-10), in combination with IL-2, IL-5, or both. Two clones produced only Th1 cytokines, and none produced exclusively Th2 cytokines. Although IL-4 was not detected in cell culture supernatants, IL-4 mRNA was detected by polymerase chain reaction amplification in two of six clones. There were no differences between the cytokine profiles of alpha beta and gamma delta T cells. A striking finding was the markedly elevated concentrations of TNF in clone supernatants, independent of the other cytokines produced. Supernatants from mycobacterium-stimulated T-cell clones, in combination with granulocyte-macrophage colony-stimulating factor, induced aggregation of bone-marrow-derived macrophages, and this effect was abrogated by antibodies to TNF. The addition of recombinant TNF to granulocyte-macrophage colony-stimulating factor markedly enhanced macrophage aggregation, indicating that TNF produced by T cells may be an important costimulus for the granulomatous host response to mycobacteria. The cytokines produced by T cells may exert immunoregulatory and immunopathologic effects and thus mediate some of the clinical manifestations of tuberculosis.

Antigens, Bacterial↗

Cytokine production at the site of disease in human tuberculosis.

Clinical and immunologic evidence suggests that tuberculous pleuritis provides a model to understand protective immune mechanisms against Mycobacterium tuberculosis. We therefore evaluated the pattern of cytokine mRNA expression and cytokine production in pleural fluid and blood of patients with tuberculous pleuritis. RNA was extracted from mononuclear cells, reverse transcribed to cDNA, and amplified by polymerase chain reaction (PCR). After normalization for T-cell cDNA, cDNA from pleural fluid cells and peripheral blood mononuclear cells (PBMC) was amplified with cytokine-specific primers. PCR product was quantified by Southern blot. For the Th1 cytokines gamma interferon (IFN-gamma) and interleukin-2 (IL-2), PCR product was greater in pleural fluid than in blood, whereas PCR product for the Th2 cytokine IL-4 was decreased in pleural fluid compared with blood. Concentrations of IFN-gamma were elevated in pleural fluid compared with serum, but IL-2, IL-4, and IL-5 were not detectable. Mean concentrations of IFN-gamma and IL-2 in supernatants of M. tuberculosis-stimulated pleural fluid cells were significantly greater than corresponding concentrations in supernatants of stimulated PBMC. In situ hybridization showed that increased IFN-gamma production by pleural fluid cells was associated with a 20- to 60-fold increase in the frequency of antigen-reactive IFN-gamma-mRNA-expressing cells. Because IL-10 can be produced by T cells and macrophages, pleural fluid cells and PBMC were normalized for beta-actin cDNA content and then amplified by PCR with IL-10-specific primers. IL-10 mRNA was greater in pleural fluid cells than in PBMC and was expressed predominantly by macrophages. IL-10 concentrations were elevated in pleural fluid versus serum. These data provide strong evidence for compartmentalization of Th1 cytokines and IL-10 at the site of disease in humans with a resistant immune response to mycobacterial infection.

Cytokines↗

Nitric oxide as putative nonadrenergic noncholinergic inhibitory transmitter in the opossum sphincter of Oddi.

The sphincter of Oddi has a typical nonadrenergic noncholinergic inhibitory innervation; however, the transmitter of this inhibition has not been identified. The aim of the present study was to evaluate whether metabolites of the L-arginine--nitric oxide synthase pathway mediate neural inhibition in the sphincter of Oddi of the opossum. Electrical field stimulation at various frequencies (3, 5, and 10 pulses/s), performed in the presence of guanethidine (10(-6) M) to exclude adrenergic responses, caused a slight, but significant excitatory response of the sphincter of Oddi. The responses were more pronounced at the duodenal side of the sphincter of Oddi than on the hepatic side. When the electrical field stimulation was repeated after blockading muscarinic receptors, using atropine (10(-6) M), a potent inhibitory response was obtained. The inhibitory response to each of the various stimulation parameters was similar. Addition of L-arginine methyl ester (L-NAME, 2 x 10(-4) M) abolished and reversed the inhibitory effect of electrical field stimulation, resulting in a potent stimulatory effect. Higher frequencies (5 and 10 pulses/s) were more potent in causing a stimulatory response than lower frequencies (3 pulses/s). The excitatory effect of electrical field stimulation was blocked or reversed to inhibition when the amino acid L-arginine (2 x 10(-3) M) was added to the bath. In a second series of experiments, the inhibitory effect of electrical field stimulation in the presence of atropine and guanethidine was not prevented after the addition of methylene blue (5 x 10(-5) M), a substance that, in vascular smooth muscle, has been demonstrated to block cyclic GMP dependent inhibitory responses.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic Fibers↗

Relationship between renal perfusion pressure and blood flow in different regions of the kidney.

The present study examined the autoregulation of blood flow in different regions of the renal cortex and medulla in volume-expanded or hydropenic anesthetized rats. Blood flow was measured in the whole kidney by electromagnetic flowmetry, in the superficial cortex with implanted fibers and external probes for laser-Doppler flowmetry, and in the deep cortex and inner and outer medulla with implanted fibers for laser-Doppler flowmetry. At renal perfusion pressure > 100 mmHg, renal blood flow, superficial cortical blood flow, and deep cortical blood flow were all very well autoregulated in both volume-expanded and hydropenic rats. Inner and outer medullary blood flow were also well autoregulated in hydropenia, but blood flow in these regions was very poorly autoregulated in volume-expanded animals. As renal perfusion pressure was decreased below 100 mmHg in volume-expanded and hydropenic animals, renal blood flow, superficial and deep cortical blood flow, and inner and outer medullary blood flow all decreased. The results of these experiments demonstrate that blood flow in both the inner and outer portions of the renal medulla of the kidney is poorly autoregulated in volume-expanded rats but well autoregulated in hydropenic animals. In contrast, blood flow in all regions of the renal cortex is well autoregulated in both volume-expanded and hydropenic animals. These results suggest that changes in resistance in the postglomerular circulation of deep nephrons are responsible for the poor autoregulation of medullary blood flow in volume expansion despite well autoregulated cortical blood flow.

Animals↗

Assessment of changes in intrarenal blood flow in conscious rats using laser-Doppler flowmetry.

The present study was designed to develop, for the first time, a method that allows long-term repeated measurements of renal cortical blood flow (CBF) and medullary blood flow (MBF) in conscious unanesthetized rats. The use of fiber-optic probes (0.5 mm diam) for the chronic measurement of renal CBF and MBF was evaluated. Basal renal cortical and medullary laser-Doppler flow (LDF) signals and the responses to intravenous bolus injections of angiotensin II (ANG II, 12.5 ng) were determined every other day for 11 days in conscious Sprague-Dawley rats (n = 9). A recovery period of 5-7 days after surgery was required before stable signals were obtained from the implanted probes. Thereafter, the fiber-optic probes gave reproducible laser-Doppler measurements of CBF and MBF for 11 days. The CBF and MBF responses to intravenous bolus injections of ANG II (12.5 ng) were also constant during this period. Chronic implantation of the fiber-optic probes caused minimal tissue damage and did not significantly alter urine concentrating ability or renal function. These findings suggest that LDF technique with chronically implanted optical fibers provides a new tool for the continuous long-term monitoring of regional blood flow in the kidney of conscious rats.

Angiotensin II↗

Expression pattern of a murine homeobox gene, Dbx, displays extreme spatial restriction in embryonic forebrain and spinal cord.

Homeobox genes specify regional identity during development. A homeobox sequence that we have named Dbx was isolated from 13.5-day embryonic mouse telencephalon cDNA. The Dbx homeodomain shows highest sequence homology to Drosophila H2.0 and chicken CHox E. We report here the expression pattern of Dbx during mouse embryogenesis. In situ hybridization analyses indicate that Dbx is expressed exclusively within the embryonic central nervous system in a highly restricted manner. Dbx transcripts are detected within a region of the prospective cerebral cortex of the midgestation telencephalon. Dbx is also expressed in the diencephalon as well as in two thin continuous columns of neuroblasts within the hindbrain and spinal cord. This expression is limited to regions of active mitosis. Dbx may act to specify subsets of neuroblasts during the development of the central nervous system.

Amino Acid Sequence↗

Cytokine production induced by Mycobacterium tuberculosis lipoarabinomannan. Relationship to chemical structure.

Lipoarabinomannan (LAM), a major cell wall component of Mycobacterium tuberculosis, exhibits a wide spectrum of immunoregulatory effects. To identify cytokines produced by human PBMC in response to LAM, we used PCR amplification to detect cytokine mRNA. LAM-induced transcription of mRNA for cytokines characteristically produced by macrophages, including TNF, granulocyte-macrophage-CSF, IL-1 alpha, IL-1 beta, IL-6, IL-8, and IL-10. In contrast, LAM did not induce transcription of mRNA for cytokines produced predominantly by lymphocytes, such as lymphotoxin, IFN-gamma, IL-2, IL-3, or IL-4. Measurement of concentrations of TNF, granulocyte-macrophage-CSF, IL-6, IL-10, IFN-gamma, IL-2, and IL-4 in cell culture supernatants indicated that cytokine release correlated with mRNA patterns. Lipomannan (LM) and phosphatidylinositol mannosides (PIM) are simpler versions of LAM. LM lacks arabinan, whereas PIM lacks both arabinan and most mannan residues. LAM, LM, and PIM induced transcription of cytokine mRNA, elicited cytokine production, and suppressed Ag-induced T cell proliferation, indicating that most of the biologic activity of LAM was associated with the phosphatidylinositol end of the molecule. In support of this conclusion, deacylation of LAM abrogated its capacity to induce cytokine production and suppress Ag-induced proliferation. The production of macrophage-derived cytokines induced by LAM may mediate clinical manifestations of tuberculosis such as fever, weight loss, and tissue necrosis, as well as immunoregulatory effects such as inhibition of Ag-induced proliferation and hyperglobulinemia.

Adult↗

Replication of patient isolates of human immunodeficiency virus type 1 in T cells: a spectrum of rates and efficiencies of entry.

Isolates of human immunodeficiency virus type 1 (HIV-1) undergo many different rates of replication, with the time course of replication being determined by the host cell and the virus. Recently, we demonstrated that the permissiveness of four CD4+ T-cell lines for the laboratory strain NL4-3 correlated with the rate and efficiency of virus entry. In this study, we have analyzed the replication of a "slow/low" isolate from the pre-AIDS period of infection and two "rapid/high" isolates from the AIDS period of infection to determine which steps in the virus life cycle determine differences in the growth characteristics of patient isolates. Differences in the growth of the patient isolates correlated with differences in entry but not postentry steps of the virus life cycle. The two rapid/high patient isolates (SF33 and SF216) underwent 50% entry in less than or equal to 0.5 hr in C8166 cells, in less than or equal to 1 hr in mitogen-stimulated peripheral blood mononuclear cells, and in greater than or equal to 2.5 hr in H9 cells. In contrast, a class 3 slow/low patient isolate required 1 hr for 50% entry into C8166 cells, 3 hr for 50% entry into peripheral blood mononuclear cells, and 5-6 hr for 50% entry into H9 cells. Entry efficiency correlated with entry rate, with the rapid/high viruses having a 2-fold higher titer and the slow/low virus having a 5-fold higher titer on C8166 than H9 cells. The laboratory strain NL4-3 displayed intermediate rates and efficiencies of entry. These data demonstrate that entry characteristics are major determinants of the pathogenic potential of patient isolates.

Acquired Immunodeficiency Syndrome↗

Probing the bradykinin receptor: mapping the geometric topography using ethers of hydroxyproline in novel peptides.

Five decapeptides were prepared, each having the generic primary sequence D-Arg0-Arg1-Pro2-Hyp3-Gly4-Thi5-Ser6-X7 -Y8-Arg9. A C-terminal beta-turn was anticipated when X was an alkyl ether of D-4-hydroxyproline in either the cis or trans geometric state and Y was either a Tic or Oic residue. Whereas cis ethers have only very weak receptor affinities, the trans ethers are significantly more potent in binding to guinea pig smooth muscle having Ki values as low as 0.16 nM. Notably, these peptides do not contain a D-aromatic amino acid at position 7 of the primary sequence.

Amino Acid Sequence↗