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Biomedical subjects

M C Chen

Publications and source records attributed to M C Chen.

At least 19 recordsLinked to original sources

Pancytopenia caused by unsuspected pernicious anemia complicating sickle cell beta-thalassemia.

We have described a a 23-year-old black woman with sickle cell beta-thalassemia who had a urinary tract infection and who was incidentally found to be pancytopenic. Although her anemia was categorized as "normocytic, normochromic" by an electronic particle counter, evaluation of the pancytopenia confirmed unsuspected pernicious anemia. Greater vigilance and a higher index of suspicion are crucial for early diagnosis of pernicious anemia in patients with other known hemoglobinopathies.

Adult

Complete nucleotide sequence and genetic organization of papaya ringspot virus RNA.

The complete nucleotide sequence of the RNA genome of papaya ringspot virus (PRSV) was determined from four overlapping cDNA clones and by direct sequencing of viral RNA. The genomic RNA is 10326 nucleotides in length, excluding the poly(A) tract, and contains one large open reading frame that starts at nucleotide positions 86 to 88 and ends at positions 10118 to 10120, encoding a polyprotein of 3344 amino acids. The highly conserved sequence AAAUAAAANANCUCAACACAACAUA at the 5' end of the RNA of PRSV and those of the other five reported potyviruses shows 80% similarity, suggesting that this region may play a common important role for potyvirus replication. Two cleavage sites of the polyprotein were determined by amino acid sequencing of the N termini of helper component (HC-Pro, amorphous inclusion) and cylindrical inclusion (CI) proteins. Other cleavage sites were predicted by analogy with the other potyviruses. The genetic organization of PRSV is similar to that of the other potyviruses except that the first protein processed from the N terminus of the polyprotein (NT protein) has an M(r) of 63K, 18K to 34K larger than those of the other potyviruses. The cleavage site for liberating the N terminus of the HC-Pro protein was found at the same location down-stream from the consensus sequence FI(V)VRG as that reported for tobacco vein mottling virus. The NT protein of potyviruses is the most variable and may be considered important for identification of individual potyviruses. The most conserved protein of potyviruses appears to be the NIb protein, the putative polymerase for the replication of the potyviral RNA. The genetic organization of PRSV RNA is tentatively proposed to be VPg-5' leader-63K NT-52K HC-Pro-46K-72K CI-6K-48K NIa-59K NIb-35K coat protein-3' non-coding region-poly(A) tract.

Amino Acid Sequence

Gastrin induction of histamine release from primary cultures of canine oxyntic mucosal cells.

Using enzyme-dispersed canine oxyntic mucosal cells, we studied regulation of histamine release from fractions in which mast cells were largely removed by density gradient. Histamine-like immunoreactivity was demonstrated using peroxidase-anti-peroxidase immunohistochemistry. Histamine-containing cells in the small cell elutriator fractions (SCEF) were further separated by albumin step density gradients. Approximately 2.5% of cells in the low density fraction (LDF) contained histamine-like immunoreactivity; this fraction was largely depleted of the more dense mast cells (0.5%). These two fractions were cultured for 48-64 h on a Matrigel substrate. The cell content of histamine and release into the medium were measured by radioenzymatic assay. Gastrin, carbachol, and forskolin increased histamine release from the LDF. The induction of histamine release by gastrin was evident within 5 min and was sustained for at least 60 min. The response to gastrin was dose dependent between concentrations of 10(-11) and 10(-8) M. In contrast, in the mast cell-enriched SCEF, basal release was higher and gastrin was without effect; however, concanavalin A stimulated and epinephrine inhibited histamine release indicating that histamine-release mechanisms were intact in this fraction. Our methods provide a preparation of low density oxyntic mucosal histamine cells that demonstrate gastrin-responsive histamine release; we speculate that enterochromaffin-like cells account for this gastrin response.

Animals

Erythrocyte sodium-lithium countertransport in Chinese: its relationship to family history of hypertension.

Rates of sodium (Na+)-stimulated lithium (Li+) efflux (Na(+)-Li+ countertransport) and ouabain-sensitive Na+ efflux (Na+ pump) were determined in erythrocytes of Chinese normotensive and hypertensive subjects. Near-maximal rate of Na(+)-Li+ countertransport was found to be significantly higher in hypertensive than normotensive subjects. No significant difference was observed for the rate of Na+ pump between them. A second series of study involved normotensive subjects without and with hypertensive parent(s) (group A and B, respectively) and hypertensive subjects (group C). We found that the rate of Na(+)-Li+ countertransport in group A was significantly lower than that of group B and C, while no difference existed between group B and C. No significant difference was observed for the rate of Na+ pump among the three groups. Our results suggested that Na(+)-Li+ countertransport activity could be a genetic marker for essential hypertension in Chinese, similar to that as proposed in Caucasians.

Adult

[Experience of surgical treatment for colorectal endometriosis: report of 6 cases].

Endometriosis is a common disease with 8-15% occurrence in women during their reproductive period. Involvement of the bowel wall occurs rather frequently and probably presents in 12-34% of patient with pelvic endometriosis. However, it is classically asymptomatic and difficult to find out. From 1977 to 1987, we had six patients of colorectal endometriosis with mainly bowel symptoms. Five of them were located at rectum and sigmoid colon, one at the hepatic flexure of colon. All of the cases developed constipation or diarrhea, and four of them had severe abdominal pain. Four cases developed rectal bleeding. Previous operation for pelvic endometriosis was noted in two cases. The detailed examination included digital examination, endoscopy, barium enema and CT scan. Suspected malignancy was the indication for surgery in 4 cases and one in rectal stenosis. Low diagnostic rate was due to the fact that endometrial tissue rarely infiltrates the mucosa. Therefore, pathology of biopsied specimen often reveals non-conclusive finding to prevent differential diagnosis. However bowel resection offers conclusive diagnosis and chances of cure. In our study, only one suspected endometriosis case received bilateral oophorectomy. The stenotic segment of rectum restored to normal caliber after operation.

Adult

Simplified continuity equation: a simple, accurate, and noninvasive method in the evaluation of aortic stenosis.

Traditional evaluation of aortic stenosis usually requires cardiac catheterization for estimation of aortic valve area by the Gorlin formula. However, it is invasive and has been shown to be inaccurate in the presence of aortic regurgitation or low cardiac output. Evaluation of aortic stenosis by Doppler echocardiography using a continuity equation has been proved to have excellent correlation with cardiac catheterization. It requires hand tracing and computer software for calculation of time velocity integral. Recently, a simplified continuity equation was introduced, which uses the peak velocities instead of time velocity integrals. It saves time and obviates the computer assistance. The purpose of this study is to evaluate its accuracy using the standard continuity equation as the reference standard. Seventy patients with pure or combined aortic stenosis were examined. There was an excellent correlation between these two methods (r = 0.979, 95% confidence interval: 0.978-0.980). The aortic valve area derived from the peak velocity method = 0.018 + 0.949 X aortic valve area derived from the time velocity integral. The difference between the two methods was 0.04 +/- 0.08 cm2 (mean +/- SD) with a 95% confidence interval of -0.12 to 0.20 cm2. Furthermore, the correlation still remained good even in the presence of significant aortic regurgitation or impaired left ventricular function. In conclusion, the simplified continuity equation is a safe, time-saving, and accurate method for the evaluation of aortic stenosis.

Adult

Vascular effects of tetramethylpyrazine: direct interaction with smooth muscle alpha-adrenoceptors.

The interaction of tetramethylpyrazine, a vasoactive ingredient of a Chinese traditional medicinal plant, with the vascular muscle alpha 1-adrenoceptors was investigated by a direct radioligand binding technique using [3H]prazosin and vascular smooth muscle microsomes isolated from dog aorta and mesenteric artery. Tetramethylpyrazine inhibited the binding of [3H]prazosin to vascular muscle membranes in a concentration-dependent manner at a suboptimal concentration of prazosin. Scatchard analysis of the effect of tetramethylpyrazine on the saturation profile of [3H]prazosin binding to vascular muscle microsomes of either arterial muscle indicated a substantial increase of Kd values (the affinity for prazosin) without a change in Bmax (maximal binding sites for prazosin). Thus, the present results provide supporting evidence that the inhibitory effect of tetramethylpyrazine on the vasoconstriction of dog mesenteric artery induced by phenylephrine in the earlier studies may be, at least, in part due to a direct action at the recognition sites of alpha 1-adrenoceptors. Amiloride and amiloride-related compounds, which shares a common pyrazine ring structure with tetramethylpyrazine and other related derivatives, also inhibits the binding of [3H]prazosin to aortic muscle microsomal membranes. Functional studies of dog saphenous vein also indicated that both tetramethylpyrazine and its ethyl derivatives inhibited the responses induced by phenylephrine and B-HT 920 in the presence and absence of extracellular Ca2+. Together with our earlier findings that amiloride also inhibits [3H]prazosin and [3H]rauwolscine binding to vascular muscle alpha 1- and alpha 2-adrenoceptors, the present radioligand binding study in canine arteries and functional study in saphenous veins suggest that the above compounds containing the pyrazine nucleus indeed interacted at the alpha-adrenoceptor sites.

Adrenergic alpha-Agonists

Inhibitory effects of tetramethyl and tetraethyl derivatives of pyrazine on dog saphenous vein.

The effects of two structurally similar pyrazine derivatives, tetramethylpyrazine (TMP) and tetraethylpyrazine (TEP) on the contractile responses of dog saphenous vein to KCl (via membrane depolarization), phenylephrine (PHE, alpha 1-adrenergic agonist), and B-HT 920 (alpha 2-adrenergic agonist) were investigated. The relaxant or inhibitory effect of TMP and TEP was most potent on KCl-induced responses and least potent on PHE-induced responses. Their effect on KCl-induced responses was more prominent at 30 mM KCl than at 100 mM KCl. In Ca(2+)-free medium, PHE and B-HT 920 elicited transient responses, which were also markedly and reversibly inhibited by TMP and TEP. Similar results were also obtained when prostaglandin F2 alpha was used as an agonist. In all four types of contractile responses involving different receptors, the inhibitory effect of TEP was consistently more potent than that of TMP. We conclude that both TMP and TEP behave as a nonselective smooth muscle relaxant having similar and multiple actions including their general interference with the processes involving both Ca2+ entry and intracellular Ca2+ release.

Animals

Preclinical evaluation of MnDPDP: new paramagnetic hepatobiliary contrast agent for MR imaging.

Manganese(II)-N,N'-dipyridoxylethylenediamine-N,N'-diacetate-5,5'-bis (phosphate) (MnDPDP) is a paramagnetic complex designed for use as a hepatobiliary agent. The T1 relaxivity of MnDPDP (2.8 [mmol/L]-1.sec-1 in aqueous solution) was similar to that of gadolinium diethylenetriaminepentaacetic acid (DTPA) (4.5 [mmol/L]-1.sec-1) and gadolinium tetraazocyclodecanetetraacetic acid (DOTA) (3.8 [mmol/L]-1.sec-1). However, in liver tissue the T1 relaxivity of MnDPDP (21.7 [mmol/L]-1.sec-1) was threefold higher than that reported for Gd-DOTA (6.7 [mmol/L]-1.sec-1). Maximum liver T1 relaxation enhancement occurred 30 minutes after injection of MnDPDP, at which time 54MnDPDP biodistribution studies indicated that 13% of total body activity was in the liver. Enhanced (MnDPDP, 50 mumol/kg) MR images showed a fivefold increase in tumor-liver contrast-to-noise ratio over baseline unenhanced images. Results of the authors' acute and subchronic toxicity studies suggest that MnDPDP will be safe at the doses necessary for clinical imaging; at 10 mumol/kg, the safety factor (LD50/effective dose) for MnDPDP is 540, significantly greater than the safety factor of Gd-DTPA (ie, 60-100).

Animals

Mitogenic response of canine fundic epithelial cells in short-term culture to transforming growth factor alpha and insulinlike growth factor I.

We report methods allowing the culture of rapidly dividing gastric epithelial cells to investigate the regulation of mucosal cell replication. Cells from canine fundic mucosa were dispersed by enzyme treatment, enriched by filtration and elutriation, and cultured on collagen gel in DMEM/F12 medium. After 48 h, greater than 95% of the cells displayed immunoreactivity with antibody to cytokeratin, an epithelial marker. The cells formed confluent monolayers by 72 h with a transmembrane resistance of 1,600 ohm.cm2 when mounted in a Ussing chamber indicating retention of epithelial cell characteristics. Calf serum (0.1-2%) produced a dose-dependent mitogenic effect evident by increases in [3H]-thymidine incorporation into acid-precipitated material and in cell number. After an 18-24-h incubation with [3H]-thymidine, approximately 55% of the cells cultured in 2% serum showed evidence of DNA synthesis by autoradiography and all of the replicating cells were cytokeratin positive. Using comparable culture conditions, a similar proportion of cells incubated for 18-24 h with bromodeoxyuridine displayed nuclear anti-bromodeoxyuridine immunoreactivity, thus indicating that over half of the cells in these cultures synthesized DNA during this period. As with serum, epidermal growth factor and transforming growth factor alpha (TGF alpha) (10 pM to 1 nM), insulin (10 nM to 1 microM) and insulinlike growth factor-I (IGF-I, 1-100 nM) increased [3H]-thymidine uptake. The greater potency of IGF-I, compared to insulin, suggests the presence of IGF-I receptors. We conclude that this culture preparation is composed of fundic mucosal epithelial cells and contains a predominance of dividing epithelial cells. EGF/TGF alpha and IGF-I are potential factors directly regulating proliferation of fundic mucosal cells.

Animals

Gastrin-histamine interactions: direct and paracrine elements.

The receptors mediating the physiologic actions of gastrin on acid secretion and growth have thus far not been localized to specific cells or fully characterized. Studies in canine fundic mucosa indicate that gastrin receptors are present on several cell types, including parietal cells and somatostatin cells. There is also increasing evidence for a gastrin-inducible pool of histamine in the fundic mucosa which is presumably stored in histamine-enterochromaffin-like cells. From the vantage point of studies in the canine fundic mucosa, the issue is no longer which cell type has the gastrin receptor but to sort out the mechanisms by which the effects of the gastrin receptors on endocrine/paracrine (histamine and somatostatin) cells and exocrine (parietal) cells are integrated to regulate secretory function and mucosal growth and differentiation.

Animals

Clinical and electrophysiological assessment of cerebral malaria.

From January 1980 to December 1990, six cases of malaria were observed; three cases were caused by plasmodium (P.) vivax and three by P. falciparum. Following a malaria episode, two cases (33.3%), developed cerebral malaria. Both of them were infected by P. falciparum. Neurological and electrodiagnostic investigations were scheduled throughout their clinical course. The first case manifested as a grand mal seizure, followed by myoclonic jerk and a comatous state. A suppression burst EEG observed before anti-malarial therapy was initiated. In the second case, a manifestation of encephalo-myelo-neuropathy was confirmed clinically and electrophysiologically. Although both cases occurred suddenly and were extremely severe, early anti-malarial therapy resulted in good responses without sequelae. The complete reversibility of the pathological event depends on early recognition and comprehensive therapy. Further, electrophysiological assessment is recommended for the detection of regional involvement in cerebral malaria.

Adult

Low probability of double integration in transformation of nonpermissive cells by polyomavirus.

The fate of polyomavirus genomes in stable transformants was examined in experiments in which rat or hamster cells were infected with mixed viral populations containing either two distinguishable wild types or a wild type plus a transformation-deficient mutant. The results demonstrate that in 90% of the cases in either situation, a single polyomavirus parental genome became integrated into the host genome. Both parents in the mixed infection were present in the same cells and both persisted in the infected cells until transformants appeared, eliminating the possibility that one virus would exclude the other in the early steps of the infection process. We believe that these results can be generalized to transformation events derived from normal single infections. Thus, contrary to previous results for the number of integration sites determined by restriction endonuclease and blot hybridization analysis, it appears that the probability for more than one integration event in transformation by polyomavirus is low (1 in 10). A reinterpretation of previous data is proposed.

Animals

Inhibition of vasoconstriction by tetramethylpyrazine: does it act by blocking the voltage-dependent Ca channel?

Using dog mesenteric arterial ring preparations, we studied the in vitro vascular effects of tetramethylpyrazine (TMP, also known as Ligustrazine), a vasoactive component derived from Ligustium Wollichii Franchat; a widely used ingredient in Chinese herbal medicine for the treatment of cardiovascular diseases. TMP had no effect on the resting force of the vascular muscle, but it caused a dose-dependent inhibition of vascular contractile responses to KCl and phenylephrine (PHE). These inhibitory effects of TMP were reversible and more prominent at lower agonist concentrations. TMP also inhibited the responses to PHE in Ca-free medium containing 50 microM EGTA suggesting the action on the release of intracellular Ca2+. Therefore, TMP is not a specific Ca-channel blocker as claimed previously. Its vasodilatory effect is mediated by the inhibition of Ca influx, as well as the release of intracellular Ca2+.

Animals

[Role of ventrolateral medulla in pressor response elicited by stimulation of abdominal vagi in cats].

The experiments were performed on 51 cats of either sex weighing 1.8-2.4 kg to investigate the role of the ventrolateral medulla in the pressor response elicited by stimulation of central ends of abdominal vagi. We observed that both the stimulation of the central ends of abdominal vagi and occlusion of one carotid artery increased the blood pressure by 17.4 +/- 1.6 mmHg (n = 51, P less than 0.01) and 14.7 +/- 1.9 mmHg (n = 19, P less than 0.01) respectively; blockade of the caudal ventrolateral medulla or trapezoid bodies with lidocaine had little effect on blood pressure and the pressor response, but blockade of the rostral ventrolateral medulla with either lidocaine or kainic acid could cause profound depression, and even abolition, of the pressor response. Moreover, application of atropine and phentolamine to the RVL severely inhibited the abdominal vagal pressor response without affecting the baroreceptor reflex. Taken together, we conclude that the RVL is a very important relay in the pathway of the abdominal vagal pressor response in which the adrenergic and cholinergic mechanisms may be involved in the RVL, and it seems that the pressor response pathway is independent of that of the baroreceptor reflex in the RVL.

Animals

Oxygen metabolites modulate prostaglandin E2 production by isolated gastric mucosal cells.

We previously found that the small cell fraction of isolated cells from canine gastric mucosa is a major producer of prostaglandin E2 (PGE2) and identified macrophages as the predominant cellular source. Prostaglandin-H synthase activity is dependent on the continuous presence of hydroperoxides. Because reactive oxygen metabolites may mediate mucosal injury in inflammatory or ischemic disease, we studied the release of PGE2 by isolated gastric cells during exposure to an oxygen metabolite-generating system, xanthine and xanthine oxidase. We found a concentration-dependent relationship between xanthine oxidase concentration and PGE2 production without cell lysis. The maximum PGE2 production stimulated by oxidants was equivalent to the maximum PGE2 response to bradykinin and A23187. The chief and parietal cell fractions produced very little PGE2 with xanthine oxidase concentrations that stimulated maximal PGE2 production in the small cell fraction. Uric acid did not stimulate PGE2 production. Catalase completely inhibited the response, while superoxide dismutase had a partial inhibitory effect. Hydrogen peroxide stimulated concentration-dependent PGE2 production with an ED50 of approximately 5 microM. We concluded that reactive oxygen metabolites stimulate PGE2 production by the small cell fraction of gastric mucosa.

Animals