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Biomedical subjects

L Lin

Publications and source records attributed to L Lin.

At least 361 records · Page 20Linked to original sources

The peptide enterostatin may produce early satiety.

The time course of feeding, grooming, exploration, and sleeping behaviors has been measured following treatment with enterostatin, the signal pentapeptide from procolipase. The peptide was injected intraperitoneally prior to presenting food, and the frequency of feeding and grooming activity, drinking, and rest or sleeping were observed at 10-s intervals for 60 min. Enterostatin did not delay the onset of feeding but shortened the time spent eating compared to saline injected controls. Conversely, grooming activity appeared earlier following enterostatin, activity was reduced, and resting behavior occurred earlier with this peptide. There were no changes in the drinking behavior. For the first hour following enterostatin, eating represented 20.8% of the time, grooming 9.2%, activity 18.3%, and rest or sleep 47.2%, with drinking making up the other 4.4%. In contrast, saline-injected animals ate for 27.1% of the time, groomed for 12.4%, were active 28.5% of the time, had sleep or rest time equal to 27.9%, and drank for 4.1% of the time. In fasted animals, the onset of grooming, the decrease in activity, and the increase in time sleeping occurred earlier than with saline. These studies support the concept that enterostatin decreases food intake by producing early satiety.

Animals↗

Genotyping and association analysis of HLA-B61 in Japanese.

The distribution of HLA-B61-related alleles, B*4002-B*4006, was examined in the Japanese population by using PCR-SSO and PCR-RFLP methods. About half of the B61-positive individuals possessed B*4002 and the remaining half possessed B*4006. In addition, these two major B61 alleles were separately associated with different HLA-C alleles: B*4002 exhibited a strong linkage disequilibrium with Cw10, whereas B*4006 was strongly associated with C blank and DR9. Amino acid residues that contribute to the serologic epitopes of the B61 group and their relationships with other HLA-B locus antigens are discussed.

Alleles↗

Substitution of a hydrophobic residue alters the conformational stability of Shaker K+ channels during gating and assembly.

A leucine residue at position 370 (L370) in 29-4 Shaker K+ channels resides within two overlapping sequence motifs conserved among most voltage-gated channels: the S4 segment and a leucine heptad repeat. Here we investigate the effects observed upon substitution of L370 with many other uncharged amino acid residues. We find that smaller or more hydrophilic residues produce greater alterations in both activation and inactivation gating than does substitution with other large hydrophobic residues. In addition, subunits containing less conservative substitutions at position 370 are restricted in their assembly with wild-type subunits and are unlikely to form homomultimeric channel complexes. Consistent with the idea that L370 influences the tertiary structure of these channels, the results indicate that L370 undergoes specific hydrophobic interactions during the conformational transitions of gating; similar interactions may take place during the folding, insertion, or assembly of Shaker K+ channel subunits.

Amino Acid Sequence↗

Ventricular adenine nucleotide translocator mRNA is upregulated in dilated cardiomyopathy.

OBJECTIVE: A disturbed energy transfer involving the adenine nucleotide translocator across the inner mitochondrial membrane has been suggested to be one specific pathogenetic mechanism in dilated cardiomyopathy. Pretranslational steady state expression of this protein in dilated cardiomyopathy was investigated. METHODS: Concentrations of adenine nucleotide translocator were quantified by solution hybridisation. The enzyme or protein expressions of citrate synthase, lactate dehydrogenase, and creatine kinase with isozymes were determined. Analysis was performed on specimens from the left and right ventricles from six organ donor hearts, six explanted hearts with dilated cardiomyopathy, two explanted hearts with ischaemic cardiomyopathy, and from papillary muscles from seven patients operated on for mitral regurgitation. RESULTS: The ejection fraction in patients with mitral regurgitation was 50(10)%, significantly higher (p < 0.001) than in patients with dilated cardiomyopathy (23(5))%. In mitral regurgitation and in ischaemic cardiomyopathy left ventricular adenine nucleotide translocator mRNA concentrations did not differ from those in donor hearts. In dilated cardiomyopathy, adenine nucleotide translocator mRNA concentrations were significantly increased (p < 0.001). Upregulation was more pronounced in right ventricular than in left ventricular myocardium (p < 0.01). The lactate dehydrogenase M subunit fraction was increased to a similar degree in dilated cardiomyopathy and in mitral regurgitation (p < 0.05). Citrate synthase activity was significantly decreased only in dilated cardiomyopathy (p < 0.005). On the other hand, the creatine kinase B subunit content was significantly higher in mitral regurgitation than in dilated cardiomyopathy (p < 0.001). CONCLUSIONS: Despite signs of increased anaerobic and depressed oxidative capacities, dilated cardiomyopathy was specifically characterised by pretranslational upregulation of adenine nucleotide translocator.

Adolescent↗

Increased expression of the lactate dehydrogenase M subunit in myocardial regions with decreased thallium uptake.

OBJECTIVE: In ischaemic heart disease, the heart muscle is subjected to repeated episodes of regional ischaemia or to a constant underperfusion. The purpose of the present investigation was to study the myocardial metabolic adaptation to this stress. METHODS: Eighteen male patients with ischaemic heart disease were studied by biopsies taken from the left ventricular septum during bypass surgery. Citrate synthase, total lactate dehydrogenase and its H and M subunits, coenzyme Q10, and myoglobin were determined in all biopsies. Concentrations of ATP, ADP, and AMP were determined and energy charge calculated in the biopsies from the patients with ischaemic heart disease. Biopsies from the septal region of hearts obtained from brain dead kidney and liver donors were used as reference and preoperative myocardial thallium scintigraphy was performed in the patients with ischaemic heart disease to relate the myocardial biochemical markers to thallium uptake at the biopsy site. RESULTS: Myocardial activities of citrate synthase as well as contents of coenzyme Q10 and myoglobin in patients with ischaemic heart disease were not different from those of the reference group, and no linear relation was found between these three markers on the one hand and thallium uptake on the other. The energy charge was directly related and the M subunit of lactate dehydrogenase inversely related to the thallium uptake. CONCLUSION: The results suggest an absence of adaptation to ischaemia in terms of increased myocardial oxidative capacity and O2 transport and storage capacity. Furthermore, it is indicated that a stressed energy metabolism with increasing severity of ischaemic heart disease enhances anaerobic metabolism and induces a shift in myocardial lactate dehydrogenase subunit fractions.

Adolescent↗

Schizophrenic delusions among Koreans, Korean-Chinese and Chinese: a transcultural study.

In this transcultural study of schizophrenic delusions among Koreans, Korean-Chinese and Chinese, many delusions were shown to be different among the three groups in their frequency and content and the differences could be explained by sociocultural and political factors. Delusional themes sensitive to influence by sociocultural or political situations and changes seem to be 'family', 'love affairs', 'religious matters', 'economic matters', 'specific physical damage' and 'political themes.' Delusions about 'family', 'love affair', 'being raped', 'religious matters' and 'economic and business matters' were most frequent in Koreans. Delusions of 'blood-relatedness', 'longevity' and 'political themes' were most frequent in Korean-Chinese. Delusions of 'bloodsucking and brain or viscera extracted' and 'poison or being pricked by poisoned needle' were most prominent in Chinese.

Adult↗

Prostanoid-mediated vascular contraction in normotensive and hypertensive rats.

We investigated the role of prostanoids in the constrictor effect of calcium ionophore A23187, endothelin-1 and vasopressin in rings of thoracic aorta obtained from normotensive rats and rats with aortic coarctation-induced hypertension. Isometric tension was measured in aortic rings bathed in buffer with and without indomethacin (10 microM), CGS13080 (10 microM) or SQ29548 (1 microM) to inhibit cyclooxygenase and thromboxane synthase and to block TxA2-PGH2 receptors, respectively. Increases in tension elicited by A23187 and vasopressin in aortic rings from hypertensive rats exceeded responses in rings from normotensive rats. A23187-induced contractions were virtually abolished by indomethacin and SQ29548, and slightly attenuated by CGS13080. These agents also attenuated the contractions elicited by endothelin but not by vasopressin. According to these data, a prostanoid(s) agonist for TxA2-PGH2 receptors contributes to the constrictor effect of A23187 in aortic rings of hypertensive rats, and of endothelin in aortic rings of normotensive and hypertensive rats. Moreover, the expression of prostanoid-mediated contractions as it pertains to the aortic response to A23187 is greatly increased in hypertensive rats.

Animals↗

A fusion plasmid for the synthesis of lipopeptide-antigen chimeras in Escherichia coli.

Lipopeptides are potential vaccine candidates with a built-in adjuvant property. To circumvent the present chemical route of synthesis for lipopeptide-antigen conjugates, the lipoprotein property of the pColE2-P9-encoded lysis protein, CelB, was used to create the bacterial fusion plasmid, pKLY3, to produce lipopeptide-antigen chimeras in Escherichia coli. Plasmid pKLY3 is a derivative of pKK233-2 with the origin of replication of the single-stranded DNA phage, fl. Under control of the promoter, ptrc, is the 5' end of the celB gene coding for a lipoprotein signal peptide and the first five amino acids (aa) (CQANY) of the mature lysis protein. As model systems for the synthesis of small and large lipopeptide-antigens, DNA sequences coding for the P2 peptide and E. coli alkaline phosphatase (PhoA) were fused in frame to the region of celB coding for a lipoprotein signal peptide and CQANY. P2 is a 12-aa peptide including a tyrosine phosphorylation site of the epidermal growth factor receptor (EGF-R). Inducible expression of stable lipohexapeptide CQANYV, lipo-CQANY-P2, and lipo-CQANYA-PhoA, was demonstrated. Similar expression was obtained for lipo-CIEGR-P2 and lipo-CIEGRA-PhoA in which IEGR is a cleavage recognition site for the blood coagulation factor, Xa. Like QANY, IEGR is predicted to form a beta-turn structure. The presence of a lipid moiety on the products was confirmed by demonstrating the incorporation of radioactive palmitic acid and inhibition of processing by globomycin. The lipid-modified peptides were also identified by incorporation of radioactive tyrosine, and the nature of the P2 peptide was verified immunologically.(ABSTRACT TRUNCATED AT 250 WORDS)

Alkaline Phosphatase↗

Assessing the direction of causality in cross-sectional studies.

Interpretation of observational studies is difficult, particularly in cross-sectional studies, because the direction of cause and effect may be difficult to assess: Did the "outcome" affect the measured exposure level, or did the exposure affect the outcome? In this paper, the authors describe a pattern, the "checkmark pattern," which can arise in cross-sectional studies. This pattern is characterized by higher levels of the outcome in an unexposed comparison group than in some subgroups of the exposed. The pattern, if seen in certain types of observational studies, suggests that the "outcome" variable may have affected the measured exposure level. Recognition of the pattern may help the epidemiologist to decipher the causal sequence. Two examples illustrate the issues involved.

Adipose Tissue↗

IL-10, T lymphocyte inhibitor of human blood cell production of IL-1 and tumor necrosis factor.

We have identified and purified a factor that inhibits the production of IL-1 beta and TNF by stimulated human mononuclear cells. The activity is produced by the T cell lines Hut-78 and Mo constitutively under serum-free conditions. Crude conditioned media have titers of up to 100 U/ml (one unit defined as the reciprocal of the dilution producing 50% inhibition). The activity resides mainly in a single size peak of 30 to 35 kDa and an isoelectric point around 8. Other cytokines in this size range that have been reported to be inhibitory for IL-1 and TNF production include TGF-beta, IL-4, and IL-6; these factors were excluded by lack of detection, neutralizing antibody, and low activity compared with our factor. Another factor with these size and charge properties is IL-10, which inhibits T cell cytokine production. By polymerase chain reaction analysis, Mo and HuT-78 lines contain IL-10 transcripts whereas JURKAT is negative; this correlates with inhibitor bioactivity from the three lines. Use of mAb specifically showed the inhibitor to be IL-10.

Antibodies, Monoclonal↗

Effects of cyclic AMP and butyrate on cell cycle, DNA, RNA, and purine synthesis of cultured astrocytes.

Dibutyryl cyclic monophosphate (dBcAMP) has been shown to inhibit growth, and alter the morphology of astrocytes. However, the potential contribution of its hydrolytic product, butyrate, in inducing some of the changes that have been attributed to dBcAMP, is not clear. DNA, RNA, and purine synthesis were therefore studied in primary astrocyte cultures after 24 hours of exposure to varying concentrations of butyrate, dBcAMP, and agents that increase intracellular cAMP levels. Progression of cells through cell cycle was also studied by flow cytometry. Dibutyryl cAMP partially arrested cells in Go/G1 phase of cell cycle while sodium butyrate increased the percentage population of cells in G2/M phase. DNA synthesis and de novo purine synthesis were inhibited after treatment with dBcAMP, sodium butyrate, and various drugs that increase intracellular cAMP levels. RNA synthesis was increased with cAMP but was not affected by sodium butyrate. Our study shows that at millimolar concentrations, butyrate is capable of altering the cell cycle and inhibiting DNA synthesis in primary astrocyte cultures, in a manner that is similar although not identical to the effects of dBcAMP.

Animals↗

Demonstration of specific neuronal cell groups in rat brain by beta-galactosidase enzyme histochemistry.

beta-Galactosidase activity as illuminated by the indigogenic X-gal staining method has been used to demonstrate the presence of genetically modified cells carrying the reporter gene lacZ, coding for the E. coli enzyme. Endogenous activity has been assumed to be minimal since the pH optimum for the mammalian enzyme is 3.5-5.5, while the pH optimum for the E. coli enzyme (and thus of the staining procedure usually employed) is 7.3. Background staining has been reported to be limited to pericytes and a few specific neuronal cell groups. In contrast, our investigations of normal rat brain anatomy demonstrate that many specific neuronal cell groups possess endogenous beta-galactosidase activity when staining is performed at physiological pH. This suggests that background staining of endogenous beta-galactosidase activity in the rat brain has been underestimated. In addition, such specific activity would afford an additional means of identification and illustration of these cells.

Animals↗

Tandem linkage of Shaker K+ channel subunits does not ensure the stoichiometry of expressed channels.

Shaker K+ channels are multimeric, probably tetrameric proteins. Substitution of a conserved leucine residue to valine (V2) at position 370 in the Drosophila Shaker 29-4 sequence results in large alterations in the voltage dependence of gating in the expressed channels. In order to determine the effects of this mutation in hybrid channels with a fixed stoichiometry of V2 and wild-type (WT) subunits we generated cDNA constructs of two linked-monomeric subunits similar to the tandem constructs previously reported by Isacoff, E. Y., Y. N. Jan, and L. Y. Jan. (1990. Nature (Lond.). 345:530-534). In addition, we constructed a tandem cDNA containing a wild-type subunit and a truncated nonfunctional subunit (Sh102) that suppresses channel expression. We report that the voltage-dependence of the channels produced with WT and V2 subunits varied significantly with the order of the subunits in the construct (WT-V2 or V2-WT), while the WT-Sh102 construct yielded currents that were much larger than expected. These results suggest that the tandem linkage of Shaker subunits does not guarantee the stoichiometry of the expressed channel proteins.

Amino Acid Sequence↗

Mapping functional specificity in the Dfd and Ubx homeo domains.

To define homeo domain subregions that are important for embryonic targeting specificity of homeotic proteins, we generated a series of Deformed/Ultrabithorax chimeric genes in which parts of the Deformed homeo box region were substituted with Ultrabithorax sequences. Chimeric coding regions were attached to heat shock promoters and introduced into the Drosophila genome by P-element transformation. After heat-induced ectopic expression in embryos, we examined the cuticular phenotypes induced by the resulting chimeric proteins. We also tested the ability of the chimeric proteins to regulate transcription units that are normal targets of Deformed and Ultrabithorax. Our results indicate that specific amino acid residues at the amino end of the Ultrabithorax homeo domain are required to specifically regulate Antennapedia transcription; and in the context of a Deformed protein, these amino-end residues are sufficient to switch from Deformed- to Ultrabithorax-like targeting specificity. Although residues in the amino end of the homeo domain are also important in determining a Deformed-like targeting specificity, other regions of the Deformed homeo domain are also required for full activity.

Amino Acid Sequence↗

Use of 8-methoxypsoralen and long wavelength ultraviolet radiation for decontamination of platelet concentrates.

Transmission of viral diseases through blood products remains a problem in transfusion medicine. We have developed a photochemical decontamination system (PCD) for platelet concentrates (PC) utilizing treatment with long wavelength ultraviolet radiation (UVA, 320-400 nm) and 8-methoxypsorlan (8-MOP). This system is capable of inactivating 25-30 logs/hour of bacteria E. coli or S. aureus, 6 logs/hour of bacteriophage fd, 0.9 log/hour of bacteriophage R17, and 1.1 logs/hour of feline leukemia virus (FeLV) in PC. Immediately following 6 hours of PCD treatment, platelet integrity and function of PCD-treated and control PC were equivalent. After overnight storage, PCD-treated and control PC platelet properties were equal, but there was a slight reduction in TXB-2 production of PCD-treated PC compared to controls. Following PCD treatment, PC were stored for 48 to 96 hours. Platelet counts, morphology scores, extracellular LDH levels, aggregation response, dense body (db) content, and alpha granule (alpha g) content of PCD-treated and control PC were comparable. We assessed the ability of the PCD technique to inactivate intracellular and extracellular virus, quantified the degree of DNA adduct formation in contaminating lymphocytes, and measured the inhibition of polymerase chain reaction (PCR) mediated amplification of intracellular DNA. High titers of cell-free murine cytomegalovirus added to human platelet concentrates (final concentration 10(6)) were inactivated by PCD within 30 minutes. Cat renal fibroblasts infected at high levels with feline rhinotracheitis virus (FeRTV) were seeded into PC followed by PCD treatment with inactivation of 4.8 logs of FeRTV within 10 minutes. Purified human lymphocytes were seeded into PC and treated with PCD in the presence of 3H 8-MOP. Six hours of PCD treatment resulted in the formation of 9.3 to 12.8 8-MOP adducts per 1000 base pairs (bp) of DNA. PCR amplification of a 242 bp segment at the HLA-DQ alpha locus was examined. Inhibition of PCR DNA amplification was dependent on the numbers of 8-MOP adducts formed, and no amplification was present when greater than 12 adducts per 1000 bp were formed. These studies indicate that PCD can effectively inactivate high titers of cell-associated and cell-free virus seeded into standard human PC. The efficiency of DNA adduct formation can be quantitated, and the level of 8-MOP adduct formation in lymphocytes contaminating PC is comparable to the level of adduct formation in cellular DNA reported in the absence of platelets.

Blood Component Transfusion↗

[A thin layer chromatography densitometric method for the determination of arecoline content in semen Arecae from different producing areas].

A TLC-densitometric method for the determination of arecoline in Semen Arecae (Areca catechu) was established, and arecoline content in three Semen Arecae (Imported, Hainan, Guanzhou) was determined. The method is accurate, sensitive and simple. The recovery is 102.39% and the coefficient of variation of six samplings is 1.95%. The are coline average content in the three Semen Arecae is 0.22%, 0.19%, 0.56% respectively.

Areca↗