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Biomedical subjects

K Yang

Publications and source records attributed to K Yang.

At least 199 records · Page 11Linked to original sources
PubMed1996

Inherited and acquired risk factors in colonic neoplasia and modulation by chemopreventive interventions.

The progressively abnormal development of epithelial cells prior to tumor development leads to widely differing chemopreventive approaches. The diversity of these approaches has resulted in different assays to measure the activities of the agents. To apply these assays to preclinical studies, we have developed rodent models in which different stages of evolution of colonic neoplasia are expressed. In one model mice carrying a truncated Apc allele with a nonsense mutation in exon 15 have been generated by gene targeting and embryonic stem cell technology (Apc 1638 mice). These mice develop multiple gastrointestinal lesions including adenomas and carcinomas, focal areas of high grade dysplasia (FAD) and polypoid hyperplasias with FADS. The incidence of inherited colonic neoplasms has now been modulated by a chemopreventive regimen. Colonic lesions significantly increased in Apc 1638 mice on a Western-style diet, compared to Apc 1638 mice on AIN-76A diet which has lower fat content and higher calcium and vitamin D. These studies have also been carried out in normal mice, and have demonstrated without any chemical carcinogen that a Western-style diet induced colonic tumorigenesis. Modulation of cell proliferation has also been induced by Western-style diets in other organs including mammary gland, pancreas and prostate. These findings are leading to the development of new preclinical models for evaluating the efficacy of many classes of chemopreventive agents.

Animals↗
PubMed1996

Dibutyl phthalate purged autologous bone marrow transplant in the treatment of leukemia.

It has been proved that di-N-butyl phthalate (DBP) is singular in killing leukemic cells selectively or accelerating the deterioration of residual leukemic cells in long-term marrow culture in vitro. Based on this principle, the DBP-purged autologous bone marrow transplant has been applied to the treatment of a group of 14 patients suffering from acute nonlymphocytic leukemia. After 5-10 days of in vitro co-culture of marrow cells with DBP at a concentration of 50 micrograms/ml, the recovery of total nucleated cells and the amount of CFU-GM were 67.5% and 68.1%, respectively. In all patients, the reconstitution of hematopoiesis was observed after pre-conditioning and transfusion of purged marrow cells. Among these, two patients had a relapse, two patients died from complications of transplant, one patient died from non-leukemic disease, and the others are all alive and free of disease; the mean survival time as calculated recently was 15 months. These preliminary clinical data support that marrow culture in the presence of DBP is a safe and effective measure for treating leukemia in purged autologous bone marrow transplant.

Adolescent↗
PubMed1996

Community surveillance of coronary heart disease in the Atherosclerosis Risk in Communities (ARIC) Study: methods and initial two years' experience.

The community surveillance component of the Atherosclerosis Risk in Communities (ARIC) Study is designed to estimate patterns and trends of coronary heart disease (CHD) incidence, case fatality, and mortality in four U.S. communities. Community surveillance involves ongoing review of death certificates and hospital discharge records to identify CHD events in community residents aged 35-74 years. Interviews with next of kin and questionnaires completed by physicians and medical examiners or coroners were used to collect information on deaths, and review and abstraction of hospital records were used to collect information on possible fatal and nonfatal myocardial infarctions (MIs). Events were classified using standardized criteria. The initial 2-years' experience with case ascertainment and availability of information needed for classification of events is described. Average annual age-adjusted attack rates of definite MI and CHD mortality rates for blacks in two communities and whites in the four communities are presented and compared with rates based on unvalidated hospital discharge data and vital statistics. Age-adjusted rates based on ARIC classification of definite MI were lower than those based on hospital discharge diagnosis code 410 (e.g., 5.60/1000 and 11.50/1000 among Forsyth County white men, respectively). Age-adjusted rates of definite fatal CHD based on ARIC classification were similarly lower than rates based on underlying cause of death code 410; for example, Jackson black men had rates of 2.82/1000 and 4.52/1000 for definite fatal CHD and UCOD 410-414 or 429.2, respectively.

Adult↗
PubMed1996

Differences between respondents and nonrespondents in a multicenter community-based study vary by gender ethnicity. The Atherosclerosis Risk in Communities (ARIC) Study Investigators.

This study provides data on differences between respondents and nonrespondents by gender and ethnicity in a multicenter community-based study that is rarely collected and that may be useful for estimating bias in prevalence estimates in other studies. Demographic, general health, and cardiovascular risk factors were examined in black and white respondents and nonrespondents to the Atherosclerosis Risk in Communities (ARIC) Study, a prospective study investigating cardiovascular risk factors in approximately 16,000 adults that was initiated in 1986 in four U.S. communities. In one of the communities (Jackson, MS) black participants were recruited exclusively; in another (Forsyth County, NC) 12% of the eligible sample were black, whereas the samples in Washington County, MD and the northwestern suburbs of Minneapolis, MN were almost all white. Demographic and health characteristics were collected during a home interview. Subjects who subsequently agreed to complete a clinical examination were defined as respondents, while eligible participants who only took part in the home interview were considered to be nonrespondents. Approximately 75% of age-eligible individuals (45-64 years) in each community completed the home interview. In three of the communities 86-88% of those who took part in the home interview also completed the clinic examination, whereas only 65% did so in Jackson. Among white participants, response rates were similar in men and women and between communities. Among black participants, the response rates were considerably lower, particularly in men. White male respondents reported a higher socioeconomic status, better general health and a lower prevalence of cardiovascular disease and associated risk factors than white male nonrespondents. The difference between white respondents and nonrespondents were greater for men than women despite similar response rates. Among black participants, respondent/nonrespondent difference were usually of smaller magnitude or absent, particularly in women. General health status and recent hospitalization rates were almost identical in black respondents and nonrespondents. Low response rates can bias estimates of prevalence in community-based studies although differences between respondents and nonrespondents tend to exaggerate real differences between respondents and the eligible population sampled. For example, among white males 25% of respondents and 44% of nonrespondents were current smokers, yet the estimated community prevalence of smoking was 31%. In conclusion, difference observed between respondents and nonrespondents were in the expected direction, but were greater for men than women and for whites than blacks.

Bias↗
PubMed1996

Model of mouse mammary gland hyperproliferation and hyperplasia induced by a western-style diet.

Mammary glands of female C57BL/6J mice were analyzed after they were fed a Western-style diet or control AIN-76A diet. The Western-style diet contained several risk factors found in human diets in geographic regions having increased risk for breast cancer: high fat and phosphate and low calcium and vitamin D. After they were fed these diets for 8, 14, and 20 weeks, mice were sacrificed, and mammary glands were removed for morphometric and radioautographic measurements. Although after the animals were fed the Western-style diet for 8 weeks the number of terminal ducts per mouse mammary gland (NTDMG) was similar in the Western-style and control diet groups, after they were fed the Western-style diet for 14 weeks (p < 0.05) and 20 weeks (p < 0.01) the NTDMG significantly increased compared with the control group. Moreover, there was a significant increase (p < 0.01) in the tritiated thymidine labeling index of mammary terminal ductal epithelial cells after 14 and 20 weeks of Western-style diet administration. Thus the Western-style diet induced increased epithelial cell proliferation and increased NTDMG in female mice when fed during young adult growth and development. The findings raise the possibility that the ingestion of a diet with Western-style fat and phosphate content and with low calcium and vitamin D may induce similar changes during the early development of the human mammary gland.

Animals↗
PubMed1996

Pattern of 11 beta-hydroxysteroid dehydrogenase type 1 messenger ribonucleic acid expression in the ovine uterus during the estrous cycle and pregnancy.

The present study was designed to examine the pattern and cellular localization of 11 beta-hydroxysteroid dehydrogenase type 1 (11 beta-HSD1) gene expression in the ovine uterus during pregnancy and at 3 mo postpartum. High levels of 11 beta-HSD1 mRNA were detected in the endometrium from Days 60 to 143 (term = 145 days), and the levels did not change significantly during that time. The level of 11 beta-HSD1 mRNA in the endometrium was always much higher than that in the myometrium, in which the mRNA was not readily detectable throughout pregnancy; at 3 mo postpartum, 11 beta-HSD1 mRNA became undetectable in both endometrium and myometrium. Within the endometrium, intense immunoreactive 11 beta-HSD1 was localized exclusively to the luminal epithelium, and the intensity of 11 beta-HSD1 immunostaining closely followed the level of 11 beta-HSD1 mRNA. To determine whether the level of endometrial 11 beta-HSD1 mRNA was related to the status of ovarian function, tissues from non-pregnant animals at different stages of their reproductive cycle were also examined. It was found that 11 beta-HSD1 mRNA was undetectable in the endometrium of cycling animals up to Day 9 of the estrous cycle but was detectable thereafter. Taken together, these results demonstrate that within the ovine uterus the endometrium is always the dominant site of 11 beta-HSD1 gene expression in relation to the myometrium. Furthermore, the expression of 11 beta-HSD1 mRNA in the endometrium is closely related to the status of the reproductive cycle. The mRNA for 11 beta-HSD1 is highly expressed only during pregnancy and in non-pregnant animals during the late luteal phase. Since circulating levels of progesterone are elevated during both of these periods, the present findings suggest a progesterone effect on uterine 11 beta-HSD1 gene expression.

11-beta-Hydroxysteroid Dehydrogenases↗
PubMed1996

Calpain inhibitors protect against depolarization-induced neurofilament protein loss of septo-hippocampal neurons in culture.

We examined the effect of a 6 min depolarization with 60 mM KCl and 1.8, 2.8 or 5.8 mM extracellular CaCl2 on neurofilament proteins of high (NF-H), medium (NF-M) and low (NF-L) molecular weight in primary septohippocampal cultures. One day after depolarization, Western blot analyses revealed losses of all three neurofilament proteins. Increasing the extracellular calcium concentration from 1.8 to 5.8 mM CaCl2 in the presence of 60 mM KCl produced increased losses of all three neurofilament proteins to approximately 80% of control values in the absence of cell death. Calcium-dependent losses of the neurofilament proteins correlated with calcium-dependent increases in calpain 1-mediated breakdown products of alpha-spectrin. Calpain inhibitors 1 and 2, applied immediately after depolarization and made available to cultures for 24 h, reduced losses of all three neurofilament proteins to approximately 14% of control values. The protective effects of calpain inhibitors 1 and 2 were influenced by different levels of extracellular calcium. Qualitative immunohistochemical evaluations confirmed semiquantitative Western blot data on neurofilament loss and protection by calpain inhibitors 1 and 2. We propose that brief depolarization causes loss of neurofilament proteins, possibly due to calpain activation. Thus, calpain inhibitors could represent a viable strategy for preserving the cytoskeletal structure of injured neurons.

Animals↗
PubMed1996

[Effects of selenium and germanium on lipid peroxidation in rats fed with low-selenium grain].

Rats were fed with grain produced in the area prevalent of Keshan disease for 12 weeks, by adding certain amount of sodium selenite (Na2SeO3) and carboxylethylgermanium (Ge-132) to study the combined effects of selenium and germanium on lipid peroxidation and metabolism of free radicals in their bodies. Results showed selenium and germanium added to the grain could reduce the content of free radicals in rats' liver and kidney tissues, and that of lipid peroxide in their heart, liver and kidney, and increase the activities of glutathione peroxidase (GSH-Px) in their blood, in a synergic way.

Animals↗
PubMed1996

Cloning and function determination of promoter region of glucoamylase gene from Aspergillus niger T21.

A 850 bp fragment of the 5' flanking region of the glucoamylase gene (glaA) was synthesized from A. niger T21 genome using PCR. The function detection vector was constructed by fusing this fragment to E. coli hygromycin B phosphotransferase gene (hph) and was used to transform A. niger. The high hygromycin resistance transformants thus obtained verified that the synthesized fragment functioned as a promoter in filamentous fungi. Southern blot analysis showed the hph gene has been integrated into genomic DNA of A. niger transformant.

Anti-Bacterial Agents↗
PubMed1996

Construction of a brewing yeast having glucoamylase activity and its fermentation characteristics.

The brewing yeast having glucoamylase activity was constructed by integrating glucoamylase cDNA from Asapergillus niger into the genome of brewing yeast B48. The integration was achieved by cotransformation of YEP type plasmid pKG1 carrying glucoamylase expression-secretion element and was verified by Southern blot analysis. The engineered yeast was stable, and the fermentation test demonstrated that the lower residual dextrin level was obtained compared with control strain B48. Thus the fermentation rate was raised to 80.5%. No alteration of growth and brewing properties was observed. Beer quality was judged to be good.

Aspergillus niger↗
PubMed1996

Transposition of flexor pollicis brevis muscle for reconstruction of thumb opposition. Anatomical study and clinical application.

OBJECTIVE: Based on the anatomical study and clinical trial of transposition of the flexor pollicis brevis muscle (M. f. p.b.) for the reconstruction of thumb opposition, we suggested a new method for the treatment of irreparable median nerve injury which causes paralysis of the opponens pollicis and the abductor pollicis brevis muscles (M.a.p.b) and leads to loss of thumb opposition. MATERIAL AND METHODS: Anatomical study and biomechanic analysis were performed on 20 cadaveric hands and 8 patients who had been treated and followed up on an average for 12 months. RESULTS: The M.f.p.b. overlaps the M.a.p.b. for about half of its width at the muscle origins and the overlapping reduced to about 1/3 of the width at the muscle belley level. The M.f.p.b. chiefly inserted on the palmar aspect of the base of proximal phalanx. The M.a.p.b. primarily was inserted on the radial side of the first metacarpophalangeal(MP) joint, and the M.f.p.b. was entirely innervated by the deep branch of the ulnar nerve. In an attempt to increase the angle between longitudinal force lines of these two muscles for 7 degrees-9 degrees, we transferred the insertion of the M.f.p.b. to the radial side of the MP joint, so that it gives this muscle the function of opposition. Eight patients were treated and followed up on an average for 12 months. All had fine functional results. CONCLUSIONS: This method is effective, and least traumatic, and does not need transposition of another tendon.

Adult↗
PubMed1996

[The effect of anisodamine hydrochloride on globin chain synthesis in anemic mice].

We treated anemic mice with Anisodamine hydrochloride followed by Hb electrophoresis and detection of globin chain synthesis rate. We found that the synthesis of their globin chains remarkably increased and would last for approximately 10 days, While the results did not show any generation of fetal Hb, possible effect of the drug might come from the raising of alpha and beta globin chains of the adult mice.

Anemia↗
PubMed1995

International study of expert judgement on therapeutic use of benzodiazepines and other psychotherapeutic medications: II. Pharmacotherapy of anxiety disorders.

OBJECTIVE: To assemble expert clinical experience and judgement in the treatment of anxiety and related disorders in a systematic, quantitative manner. METHODS: A panel of internationally recognized Experts in treating anxiety and depression was constituted by multistage peer nomination. 90% completed a questionnaire. This report focuses on case vignettes of 7 anxiety disorders followed by questions about relevant therapeutic options. RESULTS: Panelists usually recommended both psychological and pharmacological interventions. Most favored antidepressants, usually tricyclic, for agoraphobia, panic and OCD; beta-blockers for specific social phobia; and benzodiazepines for GAD and adjustment disorder. Some Experts favored polypharmacy, usually an antidepressant and a benzodiazepine. The majority usually advocated pharmacotherapy for 6 months or more. They recommended the same duration of treatment with benzodiazepines and other medications, except for GAD. CONCLUSIONS: The responses of the Expert Panel imply that; (1) most anxiety disorders are serious and merit vigorous, prolonged pharmacotherapy; and (2) antidepressants and benzodiazepines are effective and safe for long-term treatment of these conditions. This outcome contrasts with the widespread apprehension about long-term pharmacotherapy, especially with benzodiazepines, and some regulatory views.

Anti-Anxiety Agents↗
PubMed1995

Inactivation of chloramphenicol by O-phosphorylation. A novel resistance mechanism in Streptomyces venezuelae ISP5230, a chloramphenicol producer.

Plasmid pJV4, containing a 2.4-kilobase pair insert of genomic DNA from the chloramphenicol (Cm) producer Streptomyces venezuelae ISP5230, confers resistance when introduced by transformation into the Cm-sensitive host Streptomyces lividans M252 (Mosher, R. H. Ranade, N. P., Schrempf, H., and Vining, L. C. (1990) J. Gen. Microbiol. 136, 293-301). Transformants rapidly metabolized Cm to one major product, which was isolated and purified by reversed phase chromatography. The metabolite was identified by nuclear magnetic resonance spectroscopy and mass spectrometry as 3'-O-phospho-Cm, and was shown to have negligible inhibitory activity against Cm-sensitive Micrococcus luteus. The nucleotide sequence of the S. venezuelae DNA insert in pJV4 contains an open reading frame (ORF) that encodes a polypeptide (19 kDa) with a consensus motif at its NH2 terminus corresponding to a nucleotide-binding amino acid sequence (motif A or P-loop; Walker, J. E., Saraste, M., Runswick, M. J., and Gay, N. J. (1982) EMBO J. 1, 945-951). When a recombinant vector containing this ORF as a 1.6-kilobase pair SmaI-SmaI fragment was used to transform S. lividans M252, uniformly Cm-resistant transformants were obtained. A strain of S. lividans transformed by a vector in which the ORF had been disrupted by an internal deletion yielded clones that were unable to phosphorylate Cm, and exhibited normal susceptibility to the antibiotic. The results implicate the product of the ORF from S. venezuelae as an enzymic effector of Cm resistance in the producing organism by 3'-O-phosphorylation. We suggest the trivial name chloramphenicol 3'-O-phosphotransferase for the enzyme.

Amino Acid Sequence↗
PubMed1995

Regional and temporal profiles of c-fos and nerve growth factor mRNA expression in rat brain after lateral cortical impact injury.

Lesion-induced increases in NGF mRNA are thought to be mediated by c-fos gene expression. Conversely, NGF induction of c-fos expression has been reported following administration of exogenous NGF. However, the relationship between c-fos and NGF gene expression after traumatic injury to the intact brain is not known. Thus, we applied in situ hybridization and semiquantitative reverse transcription-polymerase chain reaction (RT-PCR) methods to determine temporal profiles of c-fos and NGF mRNA expression in rat brains after controlled impact to the exposed cortex. Using alternate sections from the same rat brains, in situ hybridization studies showed that in neocortex, c-fos mRNA transiently increased at 30 min, 1 hr, and 3 hr after injury, while there were no increases of NGF mRNA at these postinjury time points. In the hippocampus, in situ hybridization showed that c-fos mRNA increased at 30 min, 1 hr and 3 hr postinjury, while NGF mRNA increased at 1 hr, 3 hr but not at 30 min after injury. RT-PCR studies in hippocampus confirmed that c-fos mRNA increased as early as 5 min after injury, peaked at 30 min postinjury, and remained elevated 5 hr postinjury. Levels of hippocampal NGF mRNA expression increased by 1 hr after injury and plateaued until 3 and 5 hr postinjury. These data are consistent with the possible regulatory role of endogenous c-fos on NGF expression following traumatic brain injury.

Animals↗