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Biomedical subjects

K Yang

Publications and source records attributed to K Yang.

At least 271 records · Page 15Linked to original sources

Morphological and morphometric measurements in colorectal mucosa of subjects at increased risk for colonic neoplasia.

Measurements of intermediate biomarkers have recently increased, attempting to provide useful information about cancer risk. We report morphological findings in rectal mucosal biopsies from patients at low risk and at high risk for colorectal cancer. Rectal biopsies were analyzed from fourteen Seventh-Day Adventist (SDA) subjects at low risk and from twenty-seven members of families with hereditary nonpolyposis colonic cancer (HNPCC) at higher risk. The following measurements were made on rectal crypts: length of crypts, numbers of cells, diameter of the surface, middle and base of the crypts and infiltration of inflammatory cells into the lamina propria. Findings indicated morphological differences in normal-appearing rectal mucosa of individuals in the HNPCC group compared with SDA subjects (P < 0.05). They included shorter crypts with fewer epithelial cells and increased cellular infiltration in the mucosa of HNPCC subjects compared with SDA subjects, suggesting minimal inflammation, and an early stage of crypt atrophy in the rectal mucosa of subjects at higher risk for colonic neoplasia.

Colonic Neoplasms↗

Effect of intracerebroventricular injection of 6-hydroxydopamine on the peripheral catecholamine and angiotensin II in SHR.

This investigation revealed that the contents of A II and NE in plasma, heart and aorta and E content in plasma were significantly increased in SHR at the age of 12th week. At the same time the systolic blood pressure of SHR was much higher than that of the age-matched WKY. The intracerebroventricular administration of 6-OHDA in SHR at the age of 8th week not only prevented the development of hypertension, but also reduced the contents of NE and E in the brain regions, heart, aorta and plasma. Simultaneously A II content in heart, aorta and plasma was decreased. These results suggested that: 1. the renin-angiotensin system and peripheral sympatho-adrenal system are overactive in SHR, 2. the overactivity of peripheral sympatho-adrenal system is dependent on the central catecholaminergic neurons, and 3. the action of sympatho-adrenal system is partly responsible for the increase of A II content in plasma, heart and aorta in SHR.

Angiotensin II↗

Hypothermia attenuates the loss of hippocampal microtubule-associated protein 2 (MAP2) following traumatic brain injury.

Traumatic brain injury (TBI) produces a tissue-specific decrease in protein levels of microtubule-associated protein 2 (MAP2), an important cross-linking component of the neuronal cytoskeleton. Because moderate brain hypothermia (30 degrees C) reduces certain neurobehavioral deficits produced by TBI, we examined the efficacy of moderate hypothermia (30 degrees C) in reversing the TBI-induced loss of MAP2 protein. Naive, sham-injured, and moderate (2.1 atm) fluid percussion-injured rats were assessed for MAP2 protein content 3 h post injury using quantitative immunoreactivity measurements. Parallel groups of sham-injured and fluid percussion-injured animals were maintained in moderate hypothermia (30 degrees C), as measured by temporalis muscle temperature, for MAP2 quantitation 3 h post injury. No difference in MAP2 levels was observed between naive and sham-injured normothermic animals. Hypothermia alone had no effect on soluble MAP2 levels in sham-injured animals compared with normothermic sham-injured controls (88.0 +/- 7.3%; p > 0.10). Fluid percussion injury dramatically reduced MAP2 levels in the normothermic group (44.3 +/- 5.9%; p < 0.0005) compared with normothermic sham-injured controls. No significant reduction of MAP2 was seen in the hypothermic injured group (95.2 +/- 4.6%; compared with hypothermic sham-injured controls, p > 0.20). Although it is premature to infer any causal link, the data suggest that the attenuation of injury-induced MAP2 loss by hypothermia may contribute to its overall neuroprotective action.

Animals↗

Alterations of protein kinase C in rat hippocampus following traumatic brain injury.

Calcium-dependent excitotoxic processes contribute significantly to pathologic responses to traumatic brain injury (TBI). TBI causes neuronal depolarization and excessive excitatory neurotransmitter release, which may lead to increases in intracellular calcium levels. However, responses of calcium-dependent enzymes such as protein kinase C (PKC) following TBI are poorly understood. Since PKC plays an important role in signal transduction and maintenance of normal neuronal function, we investigated changes in PKC activity and protein levels following fluid percussion brain injury in rats. We observed a 23.1% increase in PKC activity 1 h postinjury and 80.7% increase in PKC activity 3 h postinjury. There was no statistically significant change in PKC activity 5 min and 24 h after injury. PKC immunolabelling studies detected a significant increase in PKC levels in membrane fractions 3 h but not 1 h after injury. Thus PKC activation is transiently increased following TBI and may play an important role in pathophysiologic responses to TBI.

Animals↗

Tissue distribution of alpha 1-proteinase inhibitor messenger ribonucleic acid and its regulation by glucocorticoids in fetal and neonatal sheep.

alpha 1-Proteinase inhibitor (alpha 1-PI) controls several proteinases that play important roles during inflammation and tissue remodeling, but its function during mammalian development remains obscure. We have therefore studied the ontogeny of alpha 1-PI mRNA in selected fetal and newborn sheep tissues by Northern blotting. Furthermore, because glucocorticoids play important roles in fetal maturation and parturition in sheep, we measured the relative amounts of glucocorticoid receptor (GR) mRNA in the same tissues and compared the effect of dexamethasone (DEX) administration on alpha 1-PI mRNA levels in liver and kidney of fetal and adult sheep. In the ontogeny study, a 1.8-kb alpha 1-PI mRNA was found in fetal adrenal gland and lung at Days 60-70 but was low or undetectable in these tissues at later gestational ages. By contrast, the abundance of hepatic alpha 1-PI mRNA did not vary between Days 60 and 130 of gestation, but decreased significantly (p < 0.05) at term (Days 145-147) and in newborn lambs. In the fetal kidney, it was also present between Days 60 and 130, and its relative abundance increased significantly (p < 0.05) in term and newborn lambs. These changes did not correlate with GR mRNA abundance, which was relatively stable in all tissues except the kidney, where a significant (p < 0.05) decrease was observed in neonates.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Glands↗

Foetal endocrine maturation.

In domestic ruminants such as the sheep, birth is effected through sequential maturation of the foetal hypothalamic-pituitary-adrenal (HPA) axis, leading to the increased output of cortisol. Factors regulating foetal pituitary adrenocorticotrophin (ACTH) secretion have been delineated, and these include corticotrophin releasing hormone (CRH), arginine vasopressin, prostaglandin (PG) E2 and endogenous opioids. The pre-partum increase in foetal plasma ACTH is associated with a rise in pro-opiomelanocortin (POMC) mRNA in the foetal pars distalis, and with an altered pattern of POMC post-translational processing. Foetal adrenal activation results from an increase in ACTH receptors and enhanced coupling through the Gs protein to adenylate cyclase, and increased expression of key steroidogenic enzymes including P450c17. Cortisol modulates the mechanism by which ACTH activates foetal adrenal function, through specific glucocorticoid receptors (GR) in the foetal adrenal cortex. Although the numbers of GR change with gestation, the relative abundance of GR mRNA does not, pointing to post-translational regulatory mechanisms. Cortisol also stimulates an increase in the concentration of its own high affinity binding protein (corticosteroid binding globulin; CBG) in the foetal circulation, apparently by increasing CBG gene expression in the foetal liver, and by altering the extent of foetal CBG glycosylation in a manner that would be expected to decrease the metabolic clearance of this glycoprotein. Clear evidence for placental CRH and ACTH production is lacking in sheep, but PGE2, produced in increasing amounts by the placenta during late pregnancy, may augment the drive to HPA maturation. Aspects of the maturational pathway of cortisol biosynthesis have been described in other species, including the horse, and some comparison is made with the more detailed information currently available from species such as the sheep.

Animals↗

Optimal ventilation waveforms for estimating low-frequency respiratory impedance.

We present a broad-band optimal ventilator waveform (OVW), the concept of which was to create a computer-driven ventilator waveform containing increased energy at specific frequencies (f). Values of f were chosen such that nonlinear harmonic distortion and intermodulation were minimized. The phases at each f were then optimized such that the resulting flow waveform delivered sufficient volume to maintain gas exchange while minimizing peak-to-peak airway opening pressure. Simulations with a linear anatomically consistent branching airway model and a nonlinear viscoelastic model showed that respiratory resistance (Rrs) and elastance (Ers) estimates at 0.1-2 Hz from the OVW are far superior to those from a standard step ventilator waveform (SVW) during healthy and obstructed conditions and that the OVW reduces the influences of harmonic interactions. Using a servo-controlled oscillator, we applied individual sine waves, an OVW containing energy at 0.15625-2.4 Hz, and an SVW to healthy humans and one symptomatic asthmatic subject before and after bronchodilation. The OVW was markedly superior to the SVW and always provided smooth estimates of Rrs and Ers. Before bronchodilation in the asthmatic subject Rrs was highly elevated and Ers was markedly increased with f; after bronchodilation the level of Rrs and the f dependence of Ers decreased. Although based on results from only one asthmatic subject, these data suggest a dominant influence of airway constriction and lung inhomogeneities during asthmatic bronchoconstriction that is alleviated by bronchodilators. These and other results indicate that the OVW approach has high potential for simultaneously probing f and amplitude dependence in the mechanical properties of clinical subjects during physiological breathing conditions and perhaps during dynamic bronchoconstriction.

Adult↗

Effects of sennosides and nonanthranoid laxatives on cytochemistry of epithelial cells in rat colon.

The cytochemical effects of laxatives on rat colonic epithelial cells were studied. A total of 32 rats was divided into four groups. Three groups were treated with bisacodyl, picosulfate and sennosides for 12 weeks, and a fourth group served as control. The rectum, midcolon and cecum were studied for acidic mucins, lectin soybean agglutinin (SBA) and cytokeratin AE1. Most striking and consistent changes were found in the rectum including total acidic mucin content which significantly increased, with sulfomucin decreased and sialomucin increased in the three treatment groups. Cytokeratin AE1 expression increased on picosulfate and sennosides. SBA total binding increased on bisacodyl and picosulfate. The present findings were thought to be of functional origin and do not represent early precancerous lesions.

Animals↗

Changes in the abundance of mRNA for type-I 3 beta-hydroxysteroid dehydrogenase/delta 5-->delta 4 isomerase in the human placenta and fetal membranes during pregnancy and labor.

A local decrease in progesterone synthesis in the placenta and fetal membranes has long been proposed as a possible mechanism in the control of human labor. We have examined whether changes occur in the abundance of mRNA for 3 beta-hydroxysteroid dehydrogenase/delta 5-->delta 4 isomerase (3 beta-HSD), the enzyme which catalyzes the conversion of pregnenolone to progesterone in human placenta and fetal membranes, by Northern blot analysis using a cDNA probe to human placental type-I 3 beta-HSD, the predominant isoenzyme in the placenta. The abundance of 3 beta-HSD mRNA (1.7-kb transcript) was about 10-fold greater in term placenta than in chorio-decidua, but undetectable in total RNA from amnion. There was no change in the abundance of 3 beta-HSD mRNA in either placenta or chorio-decidua obtained after elective cesarean section at term, after preterm labor, or after term or postterm vaginal delivery. We conclude that the abundance of 3 beta-HSD mRNA does not change in the placenta or fetal membranes with labor, consistent with the view that changes in 3 beta-HSD gene expression and decreased progesterone production are unlikely to effect intrauterine paracrine/autocrine regulatory mechanisms leading to term or preterm labor in women.

Blotting, Northern↗

Synthesis, cloning and sequencing of glucoamylase cDNA from Aspergillus niger mutant T21.

Poly(A)+ RNA was isolated from Aspergillus niger T21, a glucoamylase overproducing strain and was used as template to synthesize double stranded cDNA. A cDNA library was then constructed. The E. coli transformants were screened for the glucoamylase cDNA by in situ colony hybridization with P-labeled fragment of glucoamylase gene as probe. The positive rate was 1.6%. Restriction analysis proved that 32% of the positive clones carried the inserts of 2.1 kb of full length glucoamylase cDNA. Sequence of the glucoamylase cDNA was determined and the result showed that the sequence of glucoamylase gene of the mutant T21 was almost the same as that reported previously. The high rate of glucoamylase cDNA-containing clones in the cDNA library of strain T21 provided evidence of high steady state level of glucoamylase mRNA in mycelium of mutant T21. Most likely it is one of the major causes for the high glucoamylase productivity of mutant T21.

Aspergillus niger↗

[A histopathologic and immunopathologic study of 209 malignant lymphoma cases from four regions of China: Suzhou, Nanjing, Qingdao and Shenyang].

A study was conducted in four regions of China (Suzhou, Nanjing, Qingdao and Shenyang) during the period of 18 months from Dec. 1984 to June 1986, trying to find out the characteristic features of histo- and immuno-pathology of malignant lymphomas in China and relationship with HTLV-1. Fresh specimens were collected from 209 lymphoma patients who were all newly diagnosed. There were 25 cases of Hodgkin's disease (12%), and the other 184 cases of non-Hodgkin's lymphoma (88%). These 184 cases were classified according to the Working Formulation proposed by the National Cancer Institute of USA. It was found that low grade group was 5.4% and intermediate and high grade were 48.9% and 38.0%, respectively. Follicular lymphoma was 4.3% and lymphoma of small lymphocytic type was 2.7%. Fourteen cases (7.6%) were pleomorphic type mimicking adult T-cell lymphoma reported by Japanese. Immunotyping was carried out in 162 cases of non-Hodgkin's lymphoma. The tumors with T-cell markers were 33.9%, B-cell markers 62.4%, and non-T, non-B markers 3.7%. The frequency of T-cell lymphoma cases varied from area to area. Suzhou was 45.8%, Nanjing 57.9%, Qingdao 44.4% and shenyang 11.3%. In the group studied there were only 3 cases showed HTLV-1 positive in serum with pleomorphic morphology and T-cell markers. Our findings indicate that composition of histopathologic types of malignant lymphoma in China is different from that in western countries, and the incidence of T-cell lymphoma is high in certain areas of the lower reaches of the Yangzi River.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

All-trans retinoic acid induces monocyte growth factor receptor (c-fms) gene expression in HL-60 leukemia cells.

All-trans-retinoic (ATRA) treatment of patients with acute promyelocytic leukemia results in differentiation of the malignant cells and a high complete remission rate. ATRA treatment induced granulocytic differentiation in HL-60 cells as assessed by nitroblue tetrazolium (NBT) reduction, but had no effect on non-specific esterase (NSE) straining, as expected in cells maturing along the monocytic lineage. However, our results demonstrate that ATRA (0.1-10 microM) induces expression of the c-fms (monocyte colony-stimulating factor receptor) gene in HL-60 cells. This effect was detectable after 2 days and expression was maximal at 5 days. Similar results were obtained during treatment with cis-retinoic acid (CRA), hexamethylene bisacetamide (HMBA), or dimethyl sulfoxide (DMSO). The results also demonstrate that ATRA-induced c-fms expression is potentiated by exposure to tumor necrosis factor alpha (TNF alpha) or dibutyryl cyclic adenosine monophosphate (cAMP). The induction of c-fms transcripts by ATRA is associated with induction of M-CSF-binding ability, suggesting cell surface expression of the monocyte growth factor receptor. Our results indicate that retinoic acid can induce features of both monocytic and granulocytic differentiation in HL-60 cells.

Carboxylesterase↗

Functional implication of disulfide bond, Cys250 -Cys283, in bovine chymosin.

The reduction, carboxymethylation and mercuration of disulfide bond, Cys250-Cys283, located on the surface of bovine chymosin molecule resulted in the loss of about 25% of enzyme activity, suggesting that Cys250-Cys283 is not intimately involved in catalytic mechanism. Cys250 and Cys283 were substituted with Asp. and Ser. by site- directed mutagenesis of the structural gene coding for bovine prochymosin B. All three mutants (C250D/C283S, C250D, C283S) failed to be activated to chymosin in acid, indicating that Cys250-Cys283 might have some contribution to the correct refolding of the unfolded prochymosin.

Animals↗

Precancerous lesions of the human esophagus: multiparametric study of esophageal biopsies from a high-risk population in Linxian, China.

Histopathology, morphometry, tritiated thymidine incorporation and immunohistochemistry were studied in 221 esophageal biopsies from subjects with cytologica hyperplasia in Linxian, China. A spectrum of 7 morphologic entities were found: (1) normal/near normal (NN); (2) basal cell hyperplasia 0 (BHO); (3) simple hyperplasia (SH); (4) mixed basal and spinous cell hyperplasia (MBS); (5) basal cell hyperplasia 1 (BH1); (6) dysplasia (D); and (7) non-proliferative lesion (NP). Forty percent of the biopsies had combinations of histologic types. The thickness of the epithelium was increased in SH, MBS, and BH1, but not in BHO and NP. Elongation of papillae was frequently seen in SH, MBS, BH1, and D. Papillary bleeding was very prevalent in the esophageal specimens studied. A variety of cellular changes were found in peripapillary areas especially when bleeding occurred. [3H]-thymidine labeling index was dramatically increased in the entire epithelium in dysplasia, and also increased in cell layer 3 of MBS, BH1 and D. Blood group antigen LeY and lectin WGA showed consistent positivity in cellular membranes of the squamous cells, and these changes occurred before gross morphologic alterations. These findings provide a hypothesis for the sequence of pathogenetic events leading to esophageal carcinoma, and define each step with corresponding biomarkers for cancer prevention studies.

Biopsy↗

Microtubule-associated protein 2 levels decrease in hippocampus following traumatic brain injury.

We examined microtubule-associated protein 2 (MAP2) levels in hippocampal and cortical tissue 3 h following moderate traumatic brain injury (TBI) in the rat. MAP2 levels were assayed by quantitative immunoreactivity in tissue fractions obtained from naive, sham-injured, or fluid percussion-injured animals. Tissues were homogenized in the presence of protease inhibitors (0.3 mM phenylmethylsulfonyl fluoride, PMSF), a specific calpain inhibitors (0.1 mM leupeptin), and chelators (2 mM ethylene glycol-bis-tetraacetic acid, EGTA; 1 mM ethylenedinitrilo-tetraacetic acid, EDTA) to eliminate in vitro MAP2 proteolysis during tissue processing. Compared to naive rats, sham injury had no effect on soluble MAP2 levels in either cortex (105.0 +/- 4.4% of naive value) or hippocampus (106.6 +/- 5.2% of naive value). However, TBI caused a significant (p < 0.005) decrease in hippocampal MAP2 levels (55.7 +/- 5.9% of sham-injured controls). The effect appeared to be regionally selective, since the MAP2 decrease did not occur in cortex (89.1 +/- 1.4%). The degree of MAP2 decrease in hippocampus was similar in both membrane (57.8%) and cytosolic (55.7%) fractions, ruling out the possibility of partitioning artifacts. The data suggest that sublethal alterations of neuronal structure and function caused by MAP2 degradation may play an important role in the development of TBI-induced functional deficits. Since MAP2 is exclusively associated with the cytoskeleton in somal and dendritic compartments of neurons, the pathophysiology of sublethal magnitudes of TBI may also involve dendritic and somal dysfunction.

Animals↗

Cloning of an ovine 11 beta-hydroxysteroid dehydrogenase complementary deoxyribonucleic acid: tissue and temporal distribution of its messenger ribonucleic acid during fetal and neonatal development.

Glucocorticoids promote the development of many organ systems vital for extrauterine survival, and fetal cortisol provides the trigger for birth in sheep. The activity of glucocorticoids may be influenced at a cellular level by 11 beta-hydroxysteroid dehydrogenase (11 beta-HSD), which is responsible for the interconversion of cortisol and cortisone. To examine 11 beta-HSD gene expression during fetal development, two overlapping clones which yield a 1.4 kilobase (kb) complementary DNA encoding sheep 11 beta-HSD from a liver library were isolated by using a rat 11 beta-HSD cDNA as the probe. This cDNA contains a 879 base pair open reading frame for a protein of 292 amino acids that has more than 70% sequence identity to rat and human 11 beta-HSDs. To define the tissue distribution of 11 beta-HSD messenger RNA in sheep, selected tissues were collected from one fetus at day 130 and term (approximately 145 days), and from a nonpregnant ewe. Cellular RNA was extracted and subjected to Northern blot analysis, and a single 1.8 kb transcript was detected in the fetal and adult liver, lung, hypothalamus, anterior pituitary, and placenta. This was undetectable in adrenals and kidneys, but a smaller (1.5 kb) transcript was present in fetal and adult kidney RNA. The relative abundance of 11 beta-HSD mRNA was greatest in fetal and adult livers, and it was much higher in adult liver, lung, and kidney than in the corresponding fetal tissues. To examine whether 11 beta-HSD gene expression is developmentally regulated in the fetal sheep, liver, lung, and kidney tissues were taken from fetuses at day 60-70, day 100-110, day 125-130, at term, and from newborn lambs (24-48 h old). In the lung and kidney, the relative abundance of 11 beta-HSD mRNA did not change from day 60 to term but increased in the lungs of newborn lambs. In contrast, 11 beta-HSD mRNA levels in the liver increased between day 125 and term and rose further in the newborn. Collectively, these results demonstrate that 11 beta-HSD gene expression in sheep is regulated in a tissue-specific and developmentally programmed manner.

11-beta-Hydroxysteroid Dehydrogenases↗