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Biomedical subjects

G Su

Publications and source records attributed to G Su.

At least 37 records · Page 2Linked to original sources
PubMed2000

A beta vasoactivity in vivo.

Bilateral temporoparietal hypoperfusion has been frequently observed early in the Alzheimer's disease (AD) process. The beta-amyloid (A beta) peptide is believed to play a central role in the pathogenesis of AD. In vitro experiments have shown that freshly solubilized A beta enhances constriction of cerebral and peripheral vessels. We proposed that in vivo, A beta would also have vasoactive properties. To test this hypothesis, we intraarterially infused freshly solubilized A beta 1-40 in rats and observed changes in peripheral blood pressure, cerebral blood flow, and cerebrovascular resistance. We found that infusion of A beta in vivo significantly increased the blood pressure in hypotensive rats but not in normotensive and hypertensive rats. Moreover, A beta infusion also resulted in a decreased blood flow and increased vascular resistance specifically in cerebral cortex but not in heart or kidneys. These data suggest that A beta has a direct and specific constrictive effect on cerebral vessels in vivo, which may contribute to the cerebral hypoperfusion observed early in the AD process.

Amyloid↗
PubMed2000

Regulation of Na(+)-K(+)-Cl(-) cotransporter in primary astrocytes by dibutyryl cAMP and high [K(+)](o).

In this study, we examined the Na(+)-K(+)-Cl(-) cotransporter activity and expression in rat cortical astrocyte differentiation. Astrocyte differentiation was induced by dibutyryl cAMP (DBcAMP, 0. 25 mM) for 7 days, and cells changed from a polygonal to process-bearing morphology. Basal activity of the cotransporter was significantly increased in DBcAMP-treated astrocytes (P < 0.05). Expression of an approximately 161-kDa cotransporter protein was increased by 91% in the DBcAMP-treated astrocytes. Moreover, the specific [(3)H]bumetanide binding was increased by 67% in the DBcAMP-treated astrocytes. Inhibition of protein synthesis by cyclohexamide (2-3 microgram/ml) significantly attenuated the DBcAMP-mediated upregulation of the cotransporter activity and expression. The Na(+)-K(+)-Cl(-) cotransporter in astrocytes has been suggested to play a role in K(+) uptake. In 75 mM extracellular K(+) concentration, the cotransporter-mediated K(+) influx was stimulated by 147% in nontreated cells and 79% in DBcAMP-treated cells (P < 0.05). To study whether this high K(+)-induced stimulation of the cotransporter is attributed to membrane depolarization and Ca(2+) influx, the role of the L-type voltage-dependent Ca(2+) channel was investigated. The high-K(+)-mediated stimulation of the cotransporter activity was abolished in the presence of either 0.5 or 1.0 microM of the L-type channel blocker nifedipine or Ca(2+)-free HEPES buffer. A rise in intracellular free Ca(2+) in astrocytes was observed in high K(+). These results provide the first evidence that the Na(+)-K(+)-Cl(-) cotransporter protein expression can be regulated selectively when intracellular cAMP is elevated. The study also demonstrates that the cotransporter in astrocytes is stimulated by high K(+) in a Ca(2+)-dependent manner.

Animals↗
PubMed2000

Genomic structure of the human tetratricopeptide repeat-containing gene, TTC4, from chromosome region 1p31 and mutation analysis in breast cancers.

Loss of heterozygosity (LOH) in 1p31 is a frequent genetic alteration in breast tumors indicating the site of a tumor suppressor gene. We recently isolated a new member of the human tetratricopeptide repeat-containing family of genes, TTC4, which maps to this region. Other members of this gene family have been implicated in tumorigenesis suggesting that TTC4 may represent a breast cancer tumor suppressor gene. We now report the exon/intron structure of TTC4 and single strand conformation polymorphism (SSCP) analysis of DNA from 20 sporadic breast tumors. Although polymorphic variations were identified no mutations affecting the open reading frame of TTC4 were detected. Since the overall region of chromosome 1p31 which undergoes LOH can be relatively large, excluding involvement of newly isolated genes from this region in breast cancer tumorigenesis is an important process for the successful identification of the critical gene. Understanding the structure of TTC4 now makes mutation analysis possible for other cancers and diseases that map to this region.

Breast Neoplasms↗
PubMed1999

Defects in tracheoesophageal and lung morphogenesis in Nkx2.1(-/-) mouse embryos.

NKX2.1 is a homeodomain transcriptional factor expressed in thyroid, lung, and parts of the brain. We demonstrate that septation of the anterior foregut along the dorsoventral axis, into distinct tracheal and esophageal structures, is blocked in mouse embryos carrying a homozygous targeted disruption of the Nkx2.1 locus. This is consistent with the loss of Nkx2.1 expression, which defines the dorsoventral boundary within the anterior foregut in wild-type E9 embryos. Failure in septation between the trachea and the esophagus in Nkx2.1(-/-) mice leads to the formation of a common lumen that connects the pharynx to the stomach, serving both as trachea and as esophagus, similar in phenotype to a human pathologic condition termed tracheoesophageal fistula. The main-stem bronchi bifurcate from this common structure and connect to profoundly hypoplastic lungs. The mutant lungs fail to undergo normal branching embryogenesis, consist of highly dilated sacs that are not capable of sustaining normal gas exchange functions, and lead to immediate postnatal death. In situ hybridization suggests reduced Bmp-4 expression in the mutant lung epithelium, providing a possible mechanistic clue for impaired branching. Functional deletion of Nkx2. 1 blocks pulmonary-specific epithelial cell differentiation marked by the absence of pulmonary surfactant protein gene expression. Altered expression of temporally regulated genes such as Vegf demonstrates that the lung in Nkx2.1(-/-) mutant embryos is arrested at early pseudoglandular (E11-E15) stage. These results demonstrate a critical role for Nkx2.1 in morphogenesis of the anterior foregut and the lung as well as in differentiation of pulmonary epithelial cells.

Animals↗
PubMed1999

TTC4, a novel human gene containing the tetratricopeptide repeat and mapping to the region of chromosome 1p31 that is frequently deleted in sporadic breast cancer.

The 1p31 region shows loss of heterozygosity in up to 50% of human breast cancers, indicating the presence of a tumor suppressor gene in this location. We have mapped six novel ESTs to a 15-Mb contig of yeast artificial chromosomes spanning the critical region of 1p31. One of these ESTs was localized within the contig to the region most commonly undergoing loss of heterozygosity in breast cancer. The corresponding gene sequence for this EST was established by cDNA cloning and RACE procedures. This gene is 2 kb long and contains a tetratricopeptide repeat motif and a coiled-coil domain. This family of genes has been implicated in a wide variety of functions, including tumorigenesis. This is the fourth member of the human gene family, and so we have named this gene TTC4. Northern blot analysis demonstrates a ubiquitous pattern of gene expression that includes breast tissue. A preliminary screen of human breast cancer cell lines shows that TTC4 is expressed in all cases, but SSCP analysis of the coding region of this gene following RT-PCR failed to reveal any mutations. Clearly, because of its map location, a more extensive analysis is warranted to establish whether subtle mutations are present in breast cancers.

Amino Acid Sequence↗
PubMed1999

Existence of multiple novel Gs alpha splice variants in acute leukemia patients.

The alpha subunit of the stimulatory G protein, Gs alpha, is involved in stimulation of the adenylate cyclase pathway of signal transduction. In this study, we investigated the status of the Gs alpha gene in 29 acute leukemia patients and identified three novel splice variants (designated Gs alpha L-1, Gs alpha L-2, and Gs alpha L-3), possibly derived from aberrant splicing. All of the splice variants have in-frame deletions, removing the functional domain responsible for GTPase activity of Gs alpha, and would encode truncated proteins of 160(Gs alpha L-1), 90(Gs alpha L-2) and 70(Gs alpha L-3) amino acids, respectively. The data suggest that these novel products may be implicated in an as-yet-unidentified signal transduction pathway in hematopoietic cells.

Acute Disease↗
PubMed1999

The effect of photoperiod:scotoperiod on leg weakness in broiler chickens.

Four trials were conducted to investigate whether manipulations of photoperiod:scotoperiod affected the prevalence of leg weakness in broiler chickens. Modified photoperiods were applied from 3 until 21 d of age, followed by gradual or immediate return to 23 h light. The photoperiods tested were 8, 16, 21, and 23 h light. Leg weakness was assessed by measuring walking ability by gait scoring (GS) and tibial dyschondroplasia by x-ray (TD). Foot burn, hock burn, angulation of the hock joint, and BW were also measured. In total, 4,640 birds were assessed. The responses of the birds across the four trials were consistent. Increased photoperiod was associated with increased BW and prevalence of TD. There was no clear relationship between photoperiod and GS but foot pad burns were reduced by longer photoperiod. When the data were adjusted for differences in BW, increased photoperiod was associated with increased prevalence of TD, better walking ability (GS), and fewer hock and foot pad burns. Strong correlations were found between GS and live weight, and weak correlations with hock burn and TD. Tibial dyschondroplasia was weakly correlated with BW. The linear regressions of GS on live weight, within sex, across trials, were not different, but there was a difference between sexes, with males having a higher intercept but lower slope than females. It was concluded that shorter photoperiod affected walking ability and TD, but that these effects were largely a result of BW.

Animals↗
PubMed1999

Meal feeding is more effective than early feed restriction at reducing the prevalence of leg weakness in broiler chickens.

Two trials were conducted to investigate whether manipulation of feeding pattern or early feed intake affected the prevalence of leg weakness in broiler chickens. In Trial 1, the birds were offered two, three, or four meals per day or consumed feed ad libitum. In Trial 2, a multifactorial design was used with age at start, duration of restriction, and severity of restriction as factors. The start of restrictions were at 5, 7, or 9 d, duration of restriction was 5 or 7 d, and feed was restricted to achieve 25, 50, and 75% of predicted growth during the restriction period. Ad libitum birds served as controls. Leg weakness was assessed by gait scoring (GS) and tibial dyschondroplasia (TD) by radiography. Foot burn, hock burn, angulation of the hock joint, feed consumption, and body weight gain were also assessed. The response of the birds to meal feeding was clear. Fewer meals per day was associated with less TD, less hock burn, better walking ability, lower body weight, and better feed conversion. The response of the birds to feed restriction was also clear. Earlier restriction, longer duration, and more severe level of restriction were all associated with lower prevalence of TD, better walking ability, lower body weight, and better relative growth rates and feed efficiency. However, adjusting the observations for differences in body weight removed many of the significant differences; only birds that started feed restriction earlier had less TD. From these trials, it was concluded that meal feeding can beneficially affect the prevalence of leg weakness, and that the major part of this effect is independent of changes in body weight. It was also concluded that early feed restriction reduced many aspects of leg weakness, but that these effects were mainly a result of reduced body weight. Meal feeding and early feed restriction improved feed efficiency.

Animal Feed↗
PubMed1999

Different commercial broiler crosses have different susceptibilities to leg weakness.

A trial was conducted to investigate the susceptibility of different genotypes of broilers to leg weakness. Four crosses of commercial broiler lines were assessed. Birds were reared on commercial diets at commercial stocking densities. Indices of leg weakness examined included: walking ability, tibial dyschondroplasia (TD), foot pad burn, hock burn, and angulation of the hock joint. Body weight and feed efficiency were also measured. There were small differences in BW and feed efficiency among the commercial crosses; however, there were large differences in some of the indices of leg weakness among the crosses. Three crosses had similar prevalence of TD; one cross had much less TD than the others. There were large differences in walking ability among crosses. There were also differences among crosses in the prevalence of foot pad and hock burn and angulation of the hock joint. Adjusting the observations for differences in BW did not substantially alter the findings. There were differences among genotypes regarding the correlation coefficients between walking ability and BW, walking ability and hock burn, and TD and BW. It was concluded that there were large differences in some important traits associated with leg weakness among the commercial line crosses.

Animal Husbandry↗
PubMed1999

[Stable expression and immunogenicity in a attenuated Salmonella typhi strain of coli surface antigen-6 of enterotoxigenic Escherichia coli].

A gene fragment encoding for surface antigen CS6 of enterotoxigenic of Escherichia coli has been cloned into the plasmid pXL670, a new recombinant plasmid pSS64 was obtained by transforming E. coli X6097 with asd gene deletion. A safe and effective E. coli/S. typhi bivalent candidate vaccine was constructed by introducing pSS64 into delta aroA, delta aroC, delta asd Salmonella typhi. The vaccine strain is still stable in the absence of antibiotics. Animal tests demonstrated that this strain, when administered subcutaneously in mice, could provide significant protection against the intraperitoneal challenge from wild S. typhi Ty2. Immunization of rabbit with this strain raised specific antibody responses against CS6 and Vi antigen of S. typhi. This study lays the foundation for the construction of a new E. coli/S. typhi bivalent live oral vaccine.

Animals↗
PubMed1998

[Application of chromosome painting to analysis of structural aberration in five cases].

OBJECTIVE: This article reports that competitive hybridization using entire chromosome specific libraries as probe and human genomic DNA as the competitor allows intense and specific fluorescent staining of human chromosome in metaphase. This general approach is called "chromosome painting". METHODS: The probes comprising chromosomes 2, 5, 6, 7, 13, 14, X specific libraries were used to analyse five cases which had been suspected of subtle translocation and deletion in karyotype analysis by G-banding of metaphase cells. The authors selected entire chromosome-specific DNA libraries hybridizing with the five cases. Unlabeled human genomic DNA was used to inhibit the hybridization of sequences in the library that bind to multiple chromosome. RESULTS: The target chromosome was made at least 20 times brighter parunit length than the others. Translocations and deletions were detected clearly in metaphase and were consistent with G-banding. However, the result was clearer and the detection easier, compared with G-banding. CONCLUSION: Chromosome painting is very powerful for identification of chromosome structural aberrations. Translocation and deletion involving these chromosomes can be strikingly visualized. The hybridization intensity and specificity are such that even very small portions of the involved chromosome can be detected. This technique is especially useful in settings where high-quality banding is difficult.

Adult↗
PubMed1997

The vasoactivity of A beta peptides.

We have demonstrated that freshly solubilized A beta peptides can enhance vasoconstriction by phenylephrine or endothelin of isolated rat aorta. Concentrations of peptide producing these effects (100 nM-1 microM) are much lower than those requiring toxicity to endothelial cells in culture, and effects are immediate, not requiring the prolonged time periods for aggregation necessary in A beta cell culture toxicity experiments. Pre-treatment with SOD diminishes the enhancement of vasoconstriction by A beta peptides, suggesting that the effects are partly mediated via a decrease in the nitric oxide/superoxide ratio. Enhancement of endothelin vasoconstriction is observed with A beta 1-40 and A beta 1-42, but not with A beta 25-35 even at 5 microM, again suggesting the mechanism of A beta vasoactivity is distinct from that of A beta cytotoxicity. These observations raise the possibility that A beta peptides in contact with the cerebrovasculature could result in vasoconstriction, hypoperfusion and oxygen free radical imbalance contributing to the neurodegeneration of AD.

Amyloid beta-Peptides↗
PubMed1997

[Studies of magnetic circular dichroism and absorption spectra in alpha-NisO4 x 6H2O crystal].

Alpha-NiSO4 x 6H2O crystals were studied by magnetic circular dichroism (MCD) and absorption spectra measurements in the range lambda = 185-3300nm. The results show that there are three aborption bands, of which the peaks are related to the d-d transitions from the ground state to the excited states. The weak peaks of a progression of the three members were observed between the principal structures lambda = 654nm and lambda = 713nm due to spin-orbit coupling interacion. The weak peaks of a progression of four members were also observed around the new absorption peak at lambda = 585nm in MCD spectra.

English Abstract↗
PubMed1996

Relationship of whole-blood FK506 concentrations to rejection and toxicity in liver and kidney transplants.

FK506 (tacrolimus) has been shown to be a safe and effective immunosuppressant for the prevention of organ rejection after liver and kidney transplantation. Like cyclosporine, the use of FK506 has been associated with some adverse effects such as toxicity and organ rejection. Therapeutic monitoring of the whole-blood FK506 drug concentrations has been used in an effort to determine how the concentration of FK506 in the blood is related to the development of toxicity or the risk for organ rejection. Cox regression analysis of two recent clinical trials of FK506 in patients receiving kidney and liver transplants shows a significant correlation between the whole-blood FK506 concentrations and the incidence of both toxicity and organ rejection. Because of these relationships and the pharmacokinetics of FK506, therapeutic monitoring of the whole-blood FK506 levels is expected to be helpful for minimizing the risks of both toxicity and rejection in liver and kidney transplants.

Dose-Response Relationship, Drug↗
PubMed1996

[Expression of S.sonnei form I antigen gene and V.cholerae toxin B subunit gene in S.flexneri 2a strain and investigation of their immunoprotective response in mice].

The genes encoding S. sonnei form I O antigen and V. cholerae B subunit were cloned into an expression vector containing asd gene of Streptococcus mutans by gene recombination. The final recombination plasmid was transformed into the asd mutant of S. flexneri 2a (strain T32). Analysis of LPS silver staining and western blotting indicated that the genes encoding CT-B and form I O antigen could stably express in the asd mutant T32 strain. Immune protection tests in mice showed that the recombinant strain constructed in this study could provide 100% protection against the challenge from S. flexneri 2a and S. Sonnei and also showed a good immune protection (70%) against V. cholerae. This recombinant strain has the following advantages: trivalent, stable and no vector drug resistance markers.

Animals↗
PubMed1996

Construction of a stable and non-resistant bivalent vaccine candidate strain against Shigella flexneri 2a and Shigella sonnei.

The E. coli cs3 gene coding for CFA/II antigen was site-specifically integrated into the asd gene locus of S. flexneri 2a vaccine strain T32, resulting in the inactivation of the asd gene. Meanwhile, the gene cluster for S. sonnei O antigen was cloned into a non-resistant expression vector pXL378 to construct the plasmid pXL390. By transforming the asd-mutant of the T32 strain with pXL390, the bivalent vaccine candidate strain FS01 against S. flexneri 2a and S. sonnei was finally obtained. Experiments showed that the recombinant plasmid pXL390 was very stable in the asd-T32 strain without the use of any antibiotics; the FS01 strain was genetically stable and expressed two kinds of Shigella LPS-O antigens on the surface without any enhancement of its toxicity. Animal tests demonstrated that FS01 strain, when administered subcutaneously in mice, could provide 100% protection against the intraperitoneal challenges of virulent S. flexneri 2a and S. sonnei.

Animals↗