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Biomedical subjects

Q Li

Publications and source records attributed to Q Li.

At least 937 records · Page 52Linked to original sources
PubMed1993

Cloning, functional expression and pharmacological characterization of a fourth (hSSTR4) and a fifth (hSSTR5) human somatostatin receptor subtype.

Somatostatin exerts diverse effects in various tissues upon binding its specific membrane receptors. Recently, we have cloned three different somatostatin receptor subtypes. Here we report the sequence and functional expression of a fourth and a fifth human somatostatin receptor subtype, termed hSSTR4 and hSSTR5, respectively. The hSSTR4 encodes a protein of 388 amino acids and the hSSTR5 is a protein of 364 amino acids. There is 42-60% identity among the amino acid sequences of the five human somatostatin receptor subtypes identified to date. RNA blotting studies reveal that the hSSTR4 is expressed as a single transcript of 4.8 kb in MIA PaCa-2 cells, a cell line derived from human pancreatic cancer while the hSSTR5 is undetectable in the tissues examined. The hSSTR4 and hSSTR5 transiently expressed in COS1 cells exhibit specific binding to somatostatin-14 with IC50 values of 1.6 and 0.16 nM, respectively. We also have characterized the binding affinity of various somatostatin analogues to the hSSTR4 and hSSTR5. The rank of the potency of the analogues are: somatostatin-14 = somatostatin-28 >> RC-160 >> SMS201-995 for the hSSTR4 and somatostatin-28 > somatostatin-14 >> RC-160 > SMS201-995 for the hSSTR5. These results suggest that diverse actions of somatostatin are mediated by at least five somatostatin receptor subtypes with potentially different function.

Amino Acid Sequence↗
PubMed1993

Cholesterol is poorly available for free apolipoprotein-mediated cellular lipid efflux from smooth muscle cells.

To study the mechanism for resistance of smooth muscle cells (SMC) to cholesterol efflux caused by lipid-free apolipoproteins [Komaba, A., et al. (1992) J. Biol. Chem. 267, 17560-17566], the efflux of phospholipids and cholesterol was induced from mouse peritoneal macrophages (MP) and rat aortic SMC by phospholipid/triglyceride microemulsion, by human plasma high- and low-density lipoproteins (HDLs and LDLs), and by lipid-free human apolipoprotein (apo) A-I. The efflux of both lipids by the lipid microemulsion showed essentially the same kinetic profile for these two types of cells except that the rate of phospholipid efflux was 5-6 times slower by weight than cholesterol in both cases. The same ratio of cholesterol to phospholipid was also found in the efflux to LDLs. Lipid-free apoA-I mediated cellular cholesterol efflux, but the rate was much slower from SMC than from MP. However, the rate of apoA-I-mediated phospholipid efflux was similar between these two cells generating HDL-like particles, resulting in a high phospholipid:cholesterol ratio, (4-5):1 by weight, in the lipid efflux from SMC, in contrast with (0.8-1):1 in the lipid efflux from MP. When standardized for the cellular free cholesterol, the Vmax of cholesterol efflux induced by lipid-free apoA-I was 10 times slower from SMC than from MP, but only by at most 2-fold slower when lipid microemulsion was the acceptor. Thus, free cholesterol of SMC is less available than that of MP for free apolipoprotein-mediated generation of HDLs with cellular lipids.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Two Neurospora mitochondrial plasmids encode DNA polymerases containing motifs characteristic of family B DNA polymerases but lack the sequence Asp-Thr-Asp.

We have determined the DNA sequence of the mitochondrial plasmid from Neurospora intermedia strain Fiji N6-6. The plasmid contains a 1278-codon open reading frame that is 49% identical to the open reading frame of the mitochondrial plasmid from the LaBelle strain of N. intermedia, which is known to encode a DNA-dependent DNA polymerase. The results of polymerase assays and photolabeling studies, the high degree of identity with the LaBelle plasmid polymerase, and the observation that the Fiji polymerase activity in a reaction utilizing endogenous template is not affected by removal of RNA suggest that the Fiji plasmid also encodes a DNA-dependent DNA polymerase. Comparison of regions of amino acids that are highly conserved in the two plasmid polymerases to family B polymerases reveals good correlates for the three major polymerase motifs and suggests that previously identified motifs characteristic of reverse transcriptase found in the LaBelle sequence are not significant. The polymerases encoded by the Fiji and LaBelle plasmids are unusual in that the amino acid sequence Asp-Thr-Asp, which forms the core of the third motif in family B polymerases, is not present in either Fiji or LaBelle. A version of the motif containing Thr-Thr-Asp exists in both sequences.

Amino Acid Sequence↗
PubMed1993

Molecular mimicry in Lyme disease: monoclonal antibody H9724 to B. burgdorferi flagellin specifically detects chaperonin-HSP60.

A monoclonal antibody (H9724), specific for the 41-kDa flagellar protein of the Lyme disease pathogen Borrelia burgdorferi, cross-reacts with human axons and detects one major protein in human neuroblastoma cell extracts. The homologous cross-reacting protein has now been isolated from calf adrenal and identified as chaperonin-HSP60 by N-terminal sequencing.

Amino Acid Sequence↗
PubMed1993

The results of treatment in 100 patients with limited-stage small cell lung cancer.

BACKGROUND: In an attempt to improve treatment results of small cell lung cancer (SCLC), combined induction chemotherapy and thoracic and prophylactic brain radiation therapy were administered. METHOD: From December 1980 to December 1987, 112 patients with limited-stage SCLC were treated with combination induction chemotherapy and thoracic or prophylactic brain radiation therapy; 100 were evaluable. RESULTS: The complete response rate was 40%, and complete and partial responses totaled 94%, with a 5-year survival rate of 23%. There was no difference in remission and survival rates between three-drug and four-drug induction chemotherapeutic regimens. Six chemotherapeutic courses produced longer survival than less therapy. Although the occurrence of brain metastases was no different with or without prophylactic brain radiation therapy, the 3-year survival after this procedure was improved. CONCLUSION: Treatment of limited-stage SCLC with induction chemotherapy and thoracic and prophylactic brain radiation therapy produced improved remission and survival rates.

Adult↗
PubMed1993

Fatty acyl-CoA binding activity of the nuclear thyroid hormone receptor.

Long-chain fatty acids and their acyl-CoA esters are potent inhibitors of nuclear thyroid hormone (T3) receptor in vitro. In the present study, we obtained evidence for acyl-CoA binding activity in the nuclear extract from rat liver. The activity sedimented at a position (3.5 S) identical with that of the T3 receptor, and the two activities sedimented together. Similarly, they coeluted on DEAE-Sephadex. After partial purification of the receptor, it was again inhibited strongly by acyl-CoAs. Heat stability and a partial trypsin digestion of the receptor both suggested that the action site of oleoyl-CoA overlapped the T3-binding domain of the receptor. In addition, thyroid hormone receptor beta 1, synthesized in vitro, bound oleoyl-CoA specifically and its T3-binding activity was inhibited. The dissociation constant for oleoyl-CoA binding to the partially purified receptor was 1.2 x 10(-7) M. This value as well as its molecular size distinguished the nuclear binding sites from the cytoplasmic fatty acid/acyl-CoA binding proteins. Oleoyl-CoA had no effect on the glucocorticoid receptor, another member of the nuclear hormone-receptor superfamily. From these results, we propose that thyroid hormone receptor is a specific acyl-CoA binding protein of the cell nucleus.

Acyl Coenzyme A↗
PubMed1993

Prenatal cocaine produces deficits in serotonin mediated neuroendocrine responses in adult rat progeny: evidence for long-term functional alterations in brain serotonin pathways.

Cocaine produces biochemical alterations in brain serotonin (5-HT) neurons. Since 5-HT is critical to the development of fetal 5-HT neurons and target tissues, we hypothesized that in utero exposure to cocaine could result in long-term alterations in postnatal 5-HT systems. Pregnant Sprague-Dawley rats were administered either saline or (-)cocaine (15 mg/kg, s.c., b.i.d.) from gestational day 13 to 20. Prenatal cocaine exposure did not alter litter size, gender number, or progeny birth weights. Functional alterations in serotonergic systems were determined in postnatal day (PD) 70 male progeny by measuring changes in 5-HT mediated plasma hormones following a single 8 mg/kg injection of the 5-HT releaser p-chloroamphetamine (PCA). Cocaine exposed male progeny exhibited significant reductions in adrenocorticotropic hormone (ACTH, -43%) and renin (-62%) responses to PCA. However, no alterations were observed in the corticosterone or prolactin response to PCA. In utero exposure to cocaine did not alter basal levels of ACTH, renin, corticosterone, or prolactin. There were no significant differences in the density of either hypothalamic or cortical 5-HT uptake sites. Likewise, there were no significant differences in the densities of any of the 5-HT1 receptor subtypes or in the density of 5-HT2 receptors in cortex. These data, which provide the first demonstration of deficits in 5-HT mediated neuroendocrine function in adult progeny following in utero exposure to cocaine, indicate long-term functional alterations of brain 5-HT systems.

Adrenocorticotropic Hormone↗
PubMed1993

Prenatal methamphetamine attenuates serotonin mediated renin secretion in male and female rat progeny: evidence for selective long-term dysfunction of serotonin pathways in brain.

In adult rats, methamphetamine produces biochemical alterations in brain serotonin (5-HT) neurons. Since 5-HT is critical to the development of fetal 5-HT neurons and target tissues, we hypothesized that in utero exposure to methamphetamine could result in long-term alterations in postnatal 5-HT systems. Pregnant Sprague-Dawley rats, administered either saline or (+/-)methamphetamine (5 mg/kg, s.c., b.i.d.) from gestational day 13 to 20, were divided into three treatment groups: Saline-injected/Ad Lib Fed (VEH); Saline-injected/Pair Fed (PF); and methamphetamine injected (METH). Prenatal methamphetamine exposure did not alter litter size, gender number, or progeny birth weights. Functional alterations in serotonergic systems were determined in postnatal day (PD) 70 male progeny and in PD 30 female progeny by measuring changes in 5-HT mediated increases in plasma hormones following a single injection of the 5-HT releaser p-chloroamphetamine (PCA; 8 mg/kg). Prenatal methamphetamine produced long-term marked (-30 to -62%) attenuation of plasma renin responses to PCA in male and female progeny. In contrast, no alterations were observed in the ACTH, corticosterone, or prolactin responses to PCA in male and female progeny. Prenatal methamphetamine did not alter basal levels of any hormones measured regardless of gender. No significant differences were observed in the density of cortical or hypothalamic 5-HT uptake sites, or in the density of cortical 5-HT1 or 5-HT2 receptors in male progeny. The lack of significant differences in cortical 5-HT uptake sites observed between PF and METH treated dams 2 days post-parturition indicates that methamphetamine was not neurotoxic to the pregnant dams. These data, which demonstrate longterm postnatal deficits in 5-HT mediated renin secretion, suggest selective functional alterations of brain 5-HT systems in male and female progeny exposed in utero to methamphetamine.

Analysis of Variance↗