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Biomedical subjects

M J Chen

Publications and source records attributed to M J Chen.

At least 19 recordsLinked to original sources

Alcohol and smoking in relation to the prevalence of adenomatous colorectal polyps detected at sigmoidoscopy.

Cigarette smoking has been associated with adenomatous polyps of the large bowel but not with increased risk of colorectal cancer. Giovannucci et al recently proposed a hypothesis to explain this inconsistency. A key testable aspect of the hypothesis is that smoking in the distant past increases the risk of large polyps. Questions also remain about the association between colorectal polyps and consumption of alcohol. To address these issues, we examined data from 488 cases with adenomatous polyps and 488 controls. Subjects were members of a prepaid health plan in Los Angeles who had a sigmoidoscopy in 1991-1993. As expected, the adjusted odds of polyps in current smokers compared with never-smokers was increased [odds ratio = 2.43; 95% confidence interval (CI) = 1.56-3.79]. For those who had smoked in the distant past (for example, 30 or more pack-years before 20 years ago), the adjusted odds of an adenoma > or = 1 cm, relative to nonsmokers, was 0.88 (95% CI = 0.23-3.42). The adjusted odds of polyps in those consuming > or = 46 gm per day of alcohol compared with nondrinkers was 1.50 (95% CI = 0.72-3.13). Although imprecise, these data do not support the hypothesis that past smoking increases the risk of large polyps, but our results indicate a weak association between alcohol use and risk of adenomatous polyps.

Adenomatous Polyps

Action of dexmedetomidine on rat locus coeruleus neurones: intracellular recording in vitro.

The action of dexmedetomidine on rat locus coeruleus neurones was examined using intracellular recordings from the in vitro brain slice preparation. Concentrations of dexmedetomidine from 1 to 1000 nM were tested. At 30 nM, dexmedetomidine produced complete inhibition of firing of all neurones tested (n = 21); this was associated with a 13 mV hyperpolarization (range 2.2-29.7 mV, n = 21) and a 27% reduction in input resistance (range 11.1-46.2%, n = 17). The dexmedetomidine responses reached a plateau phase between 100 and 1000 nM. Based on single-cell recordings, the hyperpolarizing potency of dexmedetomidine was found to be 6 times greater than that of clonidine (n = 10). The reversal potential for the dexmedetomidine-induced hyperpolarization was -106.9 +/- 1.7 mV (n = 9), a value similar to the K+ equilibrium potential; hyperpolarization was blocked by both CsCl and BaCl2. The effect of dexmedetomidine was antagonized by yohimbine, with a dissociation equilibrium constant of 30 nM. In contrast, prazosin, the alpha 1-, alpha 2B- and alpha 2C-adrenoceptor subtype-preferring ligand, did not inhibit the dexmedetomidine effect. Our results also show that low concentrations of oxymetazoline (10-300 nM), an alpha 2A-adrenoceptor subtype-selective drug, cause profound inhibition of neuronal activity in the locus coeruleus. These data therefore suggest that dexmedetomidine binds to alpha 2A-adrenoceptors on the cell membrane of neurones of the locus coeruleus and that this leads to opening of the inwardly rectifying K+ channels, resulting in the observed hyperpolarization of the membrane.

Adrenergic alpha-2 Receptor Agonists

Mapping the domain(s) critical for the binding of human tumor necrosis factor-alpha to its two receptors.

The extracellular domains of the two human tumor necrosis factor (TNF) receptors critical for binding TNF-alpha were examined by deletion mapping. The ligand binding capability of full-length and truncated recombinant soluble TNF receptors (TNFRs) was assessed by ligand blot analysis and their binding affinity determined by Scatchard analysis. The results showed that deletion of the fourth cysteine-rich domain of the p55 receptor (TNFR-1) did not alter ligand binding affinity significantly. Deletion of domains 3 and 4 of TNFR-1 resulted in no ligand binding, suggesting that domain 3, but not 4, of TNFR-1 binds directly to ligand. Deletion of domain 4 of TNFR-2 resulted in drastically reduced protein yield and 3-fold reduction in ligand binding affinity, while deletion of both domains 4 and 3 yielded no protein. Thus, the domain 4 of TNFR-2, but not that of TNFR-1, appears to be involved directly in binding TNF, although it is also possible that the domain 4 of TNFR-2 is involved in the correct folding of other domains. These results suggest that the modes of interaction between TNF-alpha and its dual receptors are different, providing opportunity to modulate each receptor specifically for research and therapeutic purposes.

Animals

Harvesting of the latissimus dorsi muscle: a small animal model for seroma formation.

A common complication of soft tissue dissection and muscle harvesting is seroma formation. In order to manage and understand the formation of seromas, we developed a small animal model for seromas in the Sprague Dawley rat. Skin flaps and subcutaneous tissue were elevated and the latissimus dorsi muscle was harvested in 20 animals. Eighteen of the 20 rats (90%) formed clinically significant seromas. Sixteen animals had associated skin flap necrosis and 12 required serial drainage for recurrent seromas. At necropsy, gross capsular formation occurred in all animals who developed seromas. Microscopically, a fibrous capsule enveloping the seroma was seen associated with a local chronic inflammatory cell infiltrate. We conclude: (1) Elevation of the latissimus dorsi muscle in the rat is a reliable and practical animal model for seroma formation; (2) Sequelae of clinically significant seromas are often as severe as skin flap necrosis; (3) An inflammatory reaction may be associated with seromas.

Animals

Clear cell papulosis: report of three cases of a newly recognized disease.

BACKGROUND: Clear cell papulosis is a newly described disease. Since the first report in 1987, no other cases have been reported. OBJECTIVE: Our purpose was to describe three more newly identified cases that further characterize this disease. METHODS: Formalin-fixed and paraffin-embedded biopsy specimens were used for histochemical and immunohistochemical studies. RESULTS: The three patients included two boys and, for the first time, a girl. All three had multiple white papules on the lower part of the abdomen, with or without scattered lesions along the milk lines bilaterally. The main histopathologic finding was the presence of clear cells scattered mainly among the basal cells of the acanthotic epidermis. The clear cells were variably stained by mucicarmine, colloidal iron, alcian blue (pH 2.5), periodic acid-Schiff, the anticytokeratin antibody AE1, carcinoembryonic antigen, epithelial membrane antigen, and gross cystic disease fluid protein-15. CONCLUSION: Clear cell papulosis is a unique clinicopathologic entity. The clear cells were confirmed to be sweat gland secretory cells by their positive immunostaining with gross cystic disease fluid protein-15. The latter was also present in eccrine sweat gland coil cells. However, whether the clear cells were eccrine or apocrine secretory cells could not be determined.

Biopsy

Betel quid chewing, cigarette smoking and alcohol consumption related to oral cancer in Taiwan.

A hospital-based case-control study of matched pairs was conducted to explore (a) the relationship between the use of betel quid chewing, cigarette smoking, alcohol drinking and oral cancer and (b) synergism between these factors. The case group consisted of 104 male and 3 female oral cancer patients and these were compared with 194 male and 6 female matched controls. We found by univariate analysis that alcohol consumption, smoking, betel quid chewing, educational level and occupation were associated with oral cancer. The adjusted odds ratios were to be found elevated in patients who were smoking and betel quid chewing. After adjusting for education and occupation covariates, the incidence of oral cancer was computed to be 123-fold higher in patients who smoked, drank alcohol and chewed betel quid than in abstainers. The synergistic effects of alcohol, tobacco smoke and betel quid in oral cancer were clearly demonstrated, but there was a statistically significant association between oral cancer and betel quid chewing alone. Swallowing betel quid juice (saliva extract of betel quid produced by chewing) or including unripened betel fruit in the quid both seemed to enhance the risks of contracting oral cancer.

Adolescent

Variation of iron, copper, free fatty acid content and lipoxygenase activity in peanut kernels subjected to various pretreatments and roasting.

Peanut kernels subjected to pretreatment including rehydration, blanching and dehydration, and untreated kernels were roasted at 160 degrees C for times ranging from 0 to 90 min. For both peanuts, the iron content in oil and specific lipoxygenase activity in defatted peanut flour decreased, free fatty acid content increased and copper content changed insignificantly with roasting time. Changes of iron content, lipoxygenase activity and free fatty acid content were more significant in untreated peanuts than in pretreated peanuts. At each roasting time, iron, copper and free fatty acid contents in the oils and lipoxygenase activities in the defatted flours prepared from untreated peanuts were higher than in the oils and flours prepared from pretreated peanuts.

Arachis

Visual and phonological pathways to the lexicon: evidence from Chinese readers.

In this study, we investigated the role of visual and phonological information in lexical access of Chinese characters. Homophonic English words have been the main source of stimuli for word recognition research. However, since these stimuli also often look alike, visual and phonological information may be confounded in reported experiments. In contrast, many homophonic Chinese characters are visually distinct. In addition, visually similar characters often have very different pronunciations. These characteristics allow a more controlled investigation of the roles of visual and phonological information in activation of meaning. In the present study, two types of Chinese characters were used in a semantic categorization paradigm: integrated characters, which contain strokes that are not separable; and compound characters, which contain at least two clearly identifiable components. The results show that the recognition of a Chinese integrated character depends primarily on visual information, whereas the recognition of a Chinese compound character relies on visual, phonological, and semantic information. It is concluded that visual information plays a greater role in Chinese character recognition than has previously been documented.

Attention

Conformational studies of a two-module fragment of nebulin and implications for actin association.

Nebulin, a family of giant myofibrillar proteins of 700-900 kDa, has been proposed as a length-regulating template for the thin filaments of skeletal muscle. In the present study, the conformational states of a two-module nebulin fragment (ND8) were investigated by circular dichroism, steady-state fluorescence, fluorescence lifetime, and one-dimensional and two-dimensional NMR techniques. We observed the following: (a) Contrary to the predicted high alpha-helical content by computer analysis, CD spectra of ND8 indicated only a maximum of 10% alpha-helix and 25% beta-sheet in a variety of buffers; (b) The presence of increasing concentrations of trifluoroethanol (TFE) promoted the formation of alpha-helix and ND8 contained 50% alpha-helix at 67% TFE; (c) Measurement of fluorescence lifetime, anisotropy, and CD of tyrosines in ND8 in various concentrations of TFE indicates that tyrosines are incorporated into the newly formed helical segments; (d) Preliminary correlation spectroscopy and nuclear Overhauser enhancement spectroscopy NMR spectra of ND8 confirmed the formation of alpha-helical structure and identified sites of helical segments in 30% TFE around the highly conserved tyrosine residues. These data suggest that the conformation of nebulin and its mode of interaction with actin are distinct from the helical tropomyosin.

Actins

Methylphenidate treatment following ablation-induced hemiplegia in rat: experience during drug action alters effects on recovery of function.

Two experiments examined the effects of single or multiple administrations of methylphenidate (MPH; Ritalin) and differing amounts of beam-walking trials (symptom relevant experience) during the period of drug action on recovery from hemiplegia following unilateral sensorimotor cortex ablation in rat. The first study tested multiple doses of MPH (10 mg/kg) or sterile saline given once daily, followed by four beam-walk (BW) trials at 1, 2, 3, and 6 h on 3 consecutive days. A significant and enduring enhancement of recovery was only observed 24 h after the third administration of MPH, compared to saline controls. In the second study, a single dose of MPH (10 mg/kg) or saline was administered 24 h after ablation, followed by 12 BW trials beginning 1 h and continuing at 15-min intervals until 3 h after MPH or saline administration. A significant and enduring facilitation of BW ability was produced by this single MPH treatment regimen. These data further support the importance of an interaction between symptom-relevant experience and drugs that increase norepinephrine transmission to enhance functional recovery after brain damage.

Animals

Prognostic factors after hepatectomy for hepatocellular carcinoma.

During a seven and a half year period from 1985 through June 1992, hepatic resection was carried out on 84 patients with hepatocellular carcinoma. Their ages ranged from 10 to 79, with an average of 55 years. Hepatitis B surface antigen (HbsAg) was positive in 83%, an alfafetoprotein level of more than 20 ng/dl was found in 71%, and cirrhosis was noted in 64%. Surgical mortality was 3.6% and hospital mortality 1.2%. The 1-, 3- and 5-year actuarial survival rates, excluding in-hospital deaths, were 74%, 56% and 49%, respectively. The large number of patients operated on in the early stage (52%), and Child's class A (61%) might account for the low surgical mortality and high survival rate. The favorable conditions were identified as follows; no cirrhosis, surgery in the early stage, tumor size less than 5 cm, negative HbsAg and freedom from vascular involvement. Multivariate analysis showed that only negative HbsAg had better survival.

Adolescent

Treatment of beta-thalassemia with hydroxyurea (HU)--effects of HU on globin gene expression.

A newly developed method of RT-PCR/competitive PCR for measuring the relative and absolute content of globin mRNAs as well as micro-globin chain biosynthetic assay have been used to study the alterations of globin gene expressions in the patients with beta-thalassemia pre- and post-hydroxyurea (HU) treatment. It was found for the first time that HU had the effect of enhancing beta-globin gene expression in some patients. Two cases with beta-thalassemia who were subjected to HU treatment for over two years showed a marked increase in beta-globin mRNA level and beta-globin chain synthesis, resulting in more effective erythropoiesis and the alleviation of clinical symptoms.

Adult

Sexing bovine embryos using PCR amplification of bovine SRY sequence.

This study analyses the bovine SRY DNA sequence by direct sequencing procedure, followed by the designation of the PCR primers specific for bovine SRY. Using PCR amplification of bovine SRY gene, the embryo sex was determined. The results of the embryo sex identification were confirmed after the embryo transfer and pregnancies.

Animals

Complications of splenectomy for splenic injury.

From March 1986 to October 1991, there were 97 patients undergoing splenectomy for traumatic spleen injury at Chang Gung Memorial Hospital at Kaohsiung. Their ages ranged from 6 to 73 years with a mean of 39. The most common cause was blunt abdominal trauma (94/97). Sixty-five patients received splenectomy only and thirty-two patients had other operative procedures in addition to splenectomy. The most common complication in this study was intraabdominal abscess (7/97); followed by respiratory problems (5/97); postoperative hemorrhage (3/97) and wound infection (3/97). Postsplenectomy sepsis occurred in one case. There were nine cases of in-hospital mortality. Sepsis, prolonged shock and severe head injury were the main causes of death.

Adolescent

Nebulin as an actin zipper. A two-module nebulin fragment promotes actin nucleation and stabilizes actin filaments.

Nebulin is a family of giant muscle proteins (700-900 kDa) that interact with actin to form composite thin filaments in the skeletal muscle sarcomere. This modular protein is composed predominantly of repeating sequence modules of 31-38 residues. To understand the minimum size and number of sequence modules that are required for actin interaction, we studied the behavior of a highly soluble two-module nebulin fragment ND8 that was expressed in Escherichia coli. By fluorescence spectroscopy with pyrenyl-actin and co-sedimentation assays, we observed the following. 1) ND8 greatly accelerated actin nucleation, especially in a buffer that is suboptimal for actin nucleation. The presence of ND8 abolished the lag phase of actin polymerization and increased the net extent of steady state polymerization, thereby reducing the critical concentration of actin polymerization. 2) ND8 reduced the rate of actin depolymerization and might increase the rate of elongation. 3) Cytochalasin E, which caps both ends of actin filaments, inhibited the effect of ND8 on actin polymerization and caused the depolymerization of actin-ND8 complexes. These data suggest that ND8 interacts with actin in such a fashion that it stabilizes the actin nuclei and slows the depolymerization from the ends of actin filaments. 4) The binding stoichiometry of ND8 to F-actin, as estimated by co-sedimentation assays, is 1 to 2 mol of ND8 to 1 mol of actin with an apparent dissociation constant of 20 to 40 microM. Our data suggest that nebulin-actin interaction promotes actin nucleation and stabilizes preformed actin filaments, both of which are desirable attributes of a length-regulating template for actin filaments of the skeletal muscle. Each nebulin molecule may contain as many as 100-200 actin binding domains to form a zipper-like nebulin/actin composite filament.

Actins