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Biomedical subjects

D Chen

Publications and source records attributed to D Chen.

At least 757 records · Page 42Linked to original sources
PubMed1993

Accumulative effect of two low doses of irradiation in inducing an adaptive response in human lymphocytes.

A chromosomal adaptive response to Co-60 gamma-rays in human lymphocytes was observed over a range of 1-20 cGy pre-exposure doses, with 1 cGy giving optimal reduction in chromatid breaks. A 0.5 cGy dose, which in itself did not induce an adaptive response, did so when given twice within the same cell cycle, and the magnitude of the accumulative effect was strongest when there was an interval of 6 h between the two adaptive doses and between the second adaptive dose and a challenge dose. Reductions equivalent in effect to a single 1 cGy dose were seen when a 0.5 cGy dose was given twice. Delivering two 1 cGy doses had no greater effect than did a single 1 cGy dose.

Adaptation, Physiological↗
PubMed1993

Charges, currents, and potentials in ionic channels of one conformation.

Flux through an open ionic channel is analyzed with Poisson-Nernst-Planck (PNP) theory. The channel protein is described as an unchanging but nonuniform distribution of permanent charge, the charge distribution observed (in principle) in x-ray diffraction. Appropriate boundary conditions are derived and presented in some generality. Three kinds of charge are present: (a) permanent charge on the atoms of the protein, the charge independent of the electric field; (b) free or mobile charge, carried by ions in the pore as they flux through the channel; and (c) induced (sometimes called polarization) charge, in the pore and protein, created by the electric field, zero when the electric field is zero. The permanent charge produces an offset in potential, a built-in Donnan potential at both ends of the channel pore. The system is completely solved for bathing solutions of two ions. Graphs describe the distribution of potential, concentration, free (i.e., mobile) and induced charge, and the potential energy associated with the concentration of charge, as well as the unidirectional flux as a function of concentration of ions in the bath, for a distribution of permanent charge that is uniform. The model shows surprising complexity, exhibiting some (but not all) of the properties usually attributed to single filing and exchange diffusion. The complexity arises because the arrangement of free and induced charge, and thus of potential and potential energy, varies, sometimes substantially, as conditions change, even though the channel structure and conformation (of permanent charge) is strictly constant. Energy barriers and wells, and the concomitant binding sites and binding phenomena, are outputs of the PNP theory: they are computed, not assumed. They vary in size and location as experimental conditions change, while the conformation of permanent charge remains constant, thus giving the model much of its interesting behavior.

Biophysical Phenomena↗
PubMed1993

Effects of traditional and reversed bandwidth knowledge of results on motor learning.

The effects of two types of bandwidth (BW) knowledge of results (KR) were investigated on the acquisition and immediate retention of a timing task. Traditional and reversed BW KR groups were compared with two yoked control groups. Forty-eight randomly assigned subjects completed 60 acquisition trials and 20 no-KR retention trials. Acquisition analysis indicated a greater timing accuracy for the traditional BW group in comparison to the reversed BW group. During retention, less absolute constant error was found for both BW groups than for their yoked controls. Absolute performance changes were analyzed to further differentiate the contributions of quantitative and qualitative KR available in both types of BW conditions. This analysis revealed a significant KR x Trial Type interaction. Reliable changes in performance were observed after quantitative trials for the traditional BW group, whereas for the reversed BW group, reliable changes were observed after qualitative trials. This reversed BW group finding, along with the retention accuracy findings, indicated that the qualitative information was used to learn the timing task.

Female↗
PubMed1993

Comparison of semen quality obtained by vibratory stimulation and masturbation.

Six normal males underwent both penile vibratory stimulation and masturbation in order to compare the quantity and quality of semen produced by each method. There was no significant difference in the quantity and quality of the ejaculates produced by vibratory stimulation of the penis and masturbation. In addition, biochemical analysis of the seminal fluid collected by both procedures revealed similar values between all specimens for nine organic constituents, seven inorganic constituents and seven metabolic enzymes. None of the subjects demonstrated retrograde flow of semen. These findings indicate that vibratory stimulation is a 'physiological' means of inducing ejaculation, and can produce semen of normal quality.

Ejaculation↗
PubMed1993

Molecular basis for developmental changes in interleukin-2 gene inducibility.

At least three stages in the intrathymic development of pre-T cells are demarcated by differences in the competence to express the interleukin-2 (IL-2) gene as an acute response to stimulation. IL-2 inducibility appears to be acquired relatively early, prior to T-cell receptor (TcR) gene rearrangement. It is then abrogated during the stage when cells are subject to positive and negative selection, i.e., the fate determination processes that select cells for maturation or death. IL-2 inducibility finally reappears in mature classes of thymocytes that have undergone positive selection. To provide a basis for a molecular explanation of these developmental transitions, we have examined the representation in different thymocyte subsets of a set of DNA-binding proteins implicated in IL-2 gene regulation. As the DNA-binding activities of many factors are elicited only by inductive stimuli, the cells were cultured in the presence or absence of the calcium ionophore A23187 and phorbol ester. Our results separate these factors into four regulatory classes: (i) constitutive factors, such as Oct-1 and probably Sp1, that are expressed in thymocytes at all stages; (ii) inducible factors, such as NF-kappa B and complexes binding to the region of a CD28 response element, that can be activated in all thymocytes, including those cells (CD4+ CD8+ TcRlow) that can undergo selection; (iii) inducible factors, such as NF-AT and AP-1, that can be activated in mature (CD4+ CD8- TcRhigh) and immature (CD4- CD8- TcR-) thymocytes alike but not in the transitional stages when the cells (CD4+ CD8+ TcRlow) are subject to selection; and (iv) a factor containing CREB, which can be activated in thymocytes of all developmental stages by culture but does not require specific induction. These results verify that inducible transcription factors are targets of intrathymic developmental change. They also identify NF-AT and AP-1 as factors that are particularly sensitive to the mechanism altering thymocyte responses during the stages when thymocytes may undergo positive and negative selection.

Animals↗
PubMed1993

An international comparison of case definition of severe adverse cutaneous reactions to medicines.

There is substantial intercountry variation in the proportion of cases of toxic epidermal necrolysis (TEN) and Stevens-Johnson syndrome (SJS) which are attributed to specific drugs. This study was undertaken to determine whether these differences might reflect biases in diagnosis of these conditions. A total of 138 reactions in 5 countries originally diagnosed as TEN or SJS were coded on to standardised forms. A single observer blind to the original diagnosis assessed each case according to specified criteria. This observer's diagnoses were compared with the original diagnoses. Overall, 111 of the 138 cases had information adequate for assessment. The blinded observer agreed with the diagnosis for 61% of cases where the original diagnosis was TEN and 58% of cases where the original diagnosis was SJS. There was no significant difference in rates of agreement when reactions attributed to sulphonamide antibiotics were compared with reactions attributed to other drugs. There were substantial and significant differences in percentage agreement between the blinded observer's diagnosis and the original diagnoses between countries. The lowest rates of agreement between the blinded observer and the original reports occurred in the US. Our results illustrate the difficulty in comparing reaction rates based on spontaneous reports between countries where the systems for gathering such reports vary. This illustrates the need for a minimum quantity of standard data and precise definitions of reactions if spontaneous reports of adverse reactions are to provide useful information about severe adverse skin reactions associated with drugs.

Adolescent↗
PubMed1993

Gastrectomy causes bone loss in the rat: is lack of gastric acid responsible?

Total gastrectomy or resection of the acid-producing part of the stomach (fundectomy) in the rat induced a marked and rapid reduction in bone wet weight, ash weight, and density (expressed as ash weight in mg/mm3 bone). Bone volumes were also affected but not as much. The radius, sternum, tibia, and femur were studied. Three weeks after gastrectomy the bone ash weight was reduced by almost 30% and the density by more than 25%. Maximum bone loss (approximately 40%) occurred about 6 weeks after the operation. The bone loss after gastrectomy was somewhat greater than that after fundectomy, whereas antrectomy had a marginal effect only. The percentage trabecular bone volume, calculated from morphometric analysis of histologic sections of the tibia, was greatly reduced by gastrectomy (approximately 50%), somewhat less so by fundectomy, whereas antrectomy had little effect. We set out to study whether calcium malabsorption could explain the bone loss after gastrectomy. Gastric acid is thought to facilitate the intestinal absorption of ingested calcium by mobilizing calcium from insoluble complexes in the diet. The possibility that lack of acid might contribute to the bone loss after gastrectomy was examined in experiments in which the proton pump inhibitor omeprazole was given for 4-8 weeks at such a dose (400 mumol/kg/day) that acid secretion was blocked almost completely during the period of study. This treatment was without effect on bone. However, the possibility could not be excluded that gastrectomized rats develop calcium deficiency for some reason other than lack of acid.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Effects of hypercholecystokininemia produced by pancreaticobiliary diversion on pancreatic growth and enzyme mRNA levels in starved rats.

The purpose of the present study was to examine the weight, DNA content, and enzyme mRNA levels in the pancreas in response to endogenous hypercholecystokininemia produced by pancreaticobiliary diversion (PBD) in starved rats. The results showed that PBD, which is known to increase the circulating cholecystokinin (CCK) concentration, prevented the reduction in the weight and DNA content of the pancreas after 3 days of starving, and that PBD increased the mRNA levels of amylase, chymotrypsinogen B, and procarboxypeptidase A in the pancreas of starved rats. The findings support the view that endogenous CCK plays an important role in maintaining the weight of the normal pancreas of starved rats and that it stimulates the transcription of genes coding for pancreatic exocrine enzymes.

Actins↗
PubMed1993

Enterochromaffin-like cells in rat stomach respond to short-term infusion of high doses of cholecystokinin but not to long-term, sustained, moderate hyperCCKemia caused by continuous cholecystokinin infusion or pancreaticobiliary diversion.

The histamine-producing enterochromaffin-like (ECL) cells in the oxyntic mucosa are controlled by gastrin. An acute gastrin challenge induces release and accelerated resynthesis of ECL cell histamine. Long-term stimulation with gastrin causes ECL cell hyperplasia. We set out to study whether the ECL cells respond not only to gastrin but also to cholecystokinin (CCK). A wide dose range of gastrin-14 sulfated and -17 non-sulfated and CCK-8 sulfated (CCK-8s) and non-sulfated (CCK-8) was infused intravenously to rats for 3 h. The activity of the histamine-forming enzyme was measured at termination of infusion. Gastrins and CCK-8s were equally effective in activating the enzyme, whereas sulfated CCK-8 was notably less potent than the other three peptides. Clearly, the receptor responsible for activation of the ECL cells distinguishes poorly between gastrin-17 and CCK-8s, which is in line with the characteristics of the CCK-B receptor. Moreover, neither the response to gastrin-17 nor that to CCK-8s was affected by concomitant infusion of devazepide (200 micrograms/kg/h), a selective CCK-A-receptor antagonist. One group of rats received CCK-8s continuously via a minipump. Another group of rats was subjected to pancreaticobiliary diversion (PBD), which increases the plasma CCK concentration 10- to 20-fold. The rats were killed 7 or 10 weeks later, respectively, and the stomachs were analyzed with regard to mucosal growth and ECL cell hyperplasia. HyperCCKemic rats had increased pancreatic weights but showed no signs of growth stimulation in the stomach and no ECL cell hyperplasia.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Portacaval shunt increases the trophic effect of cholecystokinin on the rat pancreas.

The trophic effect of cholecystokinin (CCK) on the pancreas was examined in portacava-shunted (PCS) rats. Exogenous CCK-8s and the CCK-A receptor antagonist devazepide were infused continuously by means of osmotic minipumps. HyperCCKemia of endogenous origin was induced by pancreaticobiliary diversion (PBD), which is known to cause growth of the pancreas. The results showed that PCS as such was without a trophic effect on the pancreas, whereas the combination of CCK-8s and PCS or PBD and PCS increased the trophic effects on the pancreas compared with CCK-8s or PBD alone. Moreover, the trophic effects of PBD and of the combination of PBD and PCS could be prevented by CCK-A receptor blockade (devazepide infusion). The results suggest that the capacity of the pancreas to respond to CCK is exaggerated--for as yet unknown reasons--after PCS.

Animals↗
PubMed1993

Acute effects of smoking during modified sham feeding in duodenal ulcer patients. An analysis of nicotine, acid secretion, gastrin, catecholamines, epidermal growth factor, prostaglandin E2, and bile acids.

Smoking is associated with an increased incidence of duodenal ulcer with a high relapse rate, and smokers tend to be slow healers. The etiology responsible for this remains unknown, and there is general disagreement as to whether smoking affects gastric secretion. The aim of the present study was to investigate both aggressive and protective factors in response to vagal stimulation induced by modified sham feeding (MSF) in duodenal ulcer patients when smoking versus not smoking. On smoking days, nicotine concentrations in plasma averaged about 15 ng/ml and were extremely high in saliva and gastric juice (> 1300 and > 800 ng/ml, respectively). MSF induced a significant decrease in intragastric pH during non-smoking (p = 0.01) but not during smoking. Acid output 1 h after MSF was lower on smoking than on non-smoking days (p = 0.02), as was volume secretion (p = 0.02). Plasma gastrin concentrations were significantly increased during MSF on non-smoking days (p = 0.04) but not on smoking days, the concentrations during the whole day being lower on smoking days (p = 0.002). Plasma catecholamine levels were unaffected by MSF, whether smoking or not. However, plasma concentrations of noradrenaline decreased during the smoking of a single cigarette (p = 0.03), whereas those of adrenaline were increased on smoking days (p = 0.02). Epidermal growth factor concentrations were decreased in gastric juice after MSF during non-smoking (p = 0.01) but not during smoking. Although prostaglandin E2 (PGE2) concentrations in gastric juice were unaffected by MSF, PGE2 output increased after MSF whether smoking or not, the increment being non-significantly less during smoking (p = 0.09).(ABSTRACT TRUNCATED AT 250 WORDS)

Bile Acids and Salts↗
PubMed1993

Hypercholecystokininemia produced by pancreaticobiliary diversion causes gastrin-like effects on enterochromaffin-like cells in the stomach of rats subjected to portacaval shunting or antrectomy.

Gastrin and possibly cholecystokinin (CCK) control the activity and growth of the histamine-containing endocrine cells, the enterochromaffin-like (ECL) cells, in the oxyntic mucosa of the rat. Portacaval shunting (PCS) is known to activate the ECL cells through as yet unknown mechanisms. PCS also exaggerates the ECL cells' response to gastrin, whereas antrectomy causes hypotrophy and hypoplasia of the ECL cells. A recent study showed that the ECL cells failed to respond to sustained hyperCCKemia caused by pancreaticobiliary diversion (PBD). In the present study we investigated whether PBD-produced hyperCCKemia influenced the effects of PCS or antrectomy on the ECL cells. The results show 1) that hyperCCKemia raised the histidine decarboxylase (HDC) activity of the ECL cells in PCS rats but not in control rats, and the CCK-A receptor blockade failed to prevent the enzyme activation; and 2) that PBD prevented the ECL cell hypoplasia and the decrease in HDC activity induced by antrectomy. The findings suggest that under special circumstances endogenous CCK may stimulate the ECL cells.

Animals↗
PubMed1993

Topically active ocular carbonic anhydrase inhibitors: novel biscarbonylamidothiadiazole sulfonamides as ocular hypotensive agents.

A novel homologous series of bis(carbonyl)amidothiadiazole sulfonamides has been synthesized for structure-activity relationship studies, and initial characterization has been performed. The goal was synthesis of thiadiazole derivatives with appropriate lipid and water solubilities for utility as topically (corneal application) active carbonic anhydrase (CA) inhibitors. This series has solubility properties and pKa which bracket those of acetazolamide--the prototypical CA inhibitor. All of these compounds are active as in vitro CA inhibitors, and are 10-25% as potent as acetazolamide as in vitro enzyme inhibitors. Two of these compounds act as ocular hypotensive agents after topical application of a single dose to the corneas of normotensive New Zealand albino rabbits. The efficacy of the lead compound of this series (in this one model) is approximately equivalent to that of topical CA inhibitors that are presently in clinical trial. None of these novel compounds reacts to an appreciable extent with free sulfhydryl groups (a predictor of toxicity). This family of compounds will be useful for future studies of ocular pharmacokinetics, as well as ocular and systemic effects of topical administration of CA inhibitors. These and future studies may lead to development of thiadiazole sulfonamides useful in the management of glaucoma.

Administration, Topical↗