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Biomedical subjects

D Hu

Publications and source records attributed to D Hu.

At least 109 records · Page 6Linked to original sources

Effects of MK-801 on vicarious trial-and-error and reversal of olfactory discrimination learning in weanling rats.

The effects of dizocilpine maleate (MK-801) on vicarious trial-and-error (VTE), and on simultaneous olfactory discrimination learning and its reversal, were observed in weanling rats. The term VTE was used by Tolman (The determiners of behavior at a choice point. Psychol. Rev. 1938;46:318-336), who described it as conflict-like behavior at a choice-point in simultaneous discrimination learning. It takes the form of head movements from one stimulus to the other, and has recently been proposed by Amsel (Hippocampal function in the rat: cognitive mapping or vicarious trial-and-error? Hippocampus, 1993;3:251-256) as related to hippocampal, nonspatial function during this learning. Weanling male rats received systemic MK-801 either 30 min before the onset of olfactory discrimination training and its reversal, or only before its reversal. The MK-801-treated animals needed significantly more sessions to acquire the discrimination and showed significantly fewer VTEs in the acquisition phase of learning. Impaired reversal learning was shown only when MK-801 was administered during the reversal-learning phase, itself, and not when it was administered throughout both phases.

Animals↗

Dermal oedema assessed by high frequency ultrasound in venous leg ulcers.

Oedema is considered a key pathogenic factor in the development of venous leg ulcers. The purpose of this study was to determine the localization of oedema in legs with ulcers. Twelve patients with 13 venous leg ulcers (one bilateral), with a duration of 7-18 months, were examined by high-frequency B-mode ultrasound scanner. This was performed at three sites in the leg (low, middle and upper sites of the lower leg). In the same group of patients, the legs without ulcers were used as controls. The echogenicity and the thickness of the whole dermis were quantified by digital image analysis; the echogenicities of the upper (papillary) and lower portions of the dermis were measured. In the upper site no significant difference was found between the legs with ulcers and controls. In the middle and low sites of legs with ulcers, the dermal echogenicities were 34% and 64% (P < 0.01) less than those in controls, and the dermal thicknesses were 0.4 mm and 0.8 mm (P < 0.01) thicker than those in controls, respectively. This indicated intradermal oedema existing in the lower part (gaiter area) of the legs with ulcers. The ratios of low echogenic pixels in the upper and lower portions of the dermis, in the middle and low sites of legs with ulcers, were 0.5 and 0.9 (P < 0.05 and P < 0.01), respectively, higher than those in controls, suggesting the papillary dermis as a preferential site of oedema formation. The present study demonstrates that in the low sites of legs with ulcers, a marked increase in oedema was seen in the papillary dermis. This may add to the understanding of the origin of leg ulcers in the gaiter area of the leg.

Aged↗

Topical tamoxifen--a potential therapeutic regime in treating excessive dermal scarring?

Abnormal dermal scarring which affects a large number of people is aesthetically disfiguring and can be functionally disabling. Existing medical and surgical strategies to prevent or to treat scars are frequently disappointing and more effective therapies are needed. Tamoxifen, which has been used extensively in the treatment of breast cancer over the last 20 years has recently been shown to inhibit the proliferation of fibroblasts cultured from keloid biopsies. Successful treatment of retroperitoneal fibrosis and desmoid tumours with tamoxifen has also been reported. We have investigated the potential of tamoxifen as an inhibitor of wound contraction, using fibroblast-populated collagen lattices as an in vitro model. From these studies we postulate that tamoxifen may have potential clinical significance in the treatment of abnormal scarring. Normal adult human skin fibroblasts were embedded within type I collagen, then medium either with or without addition of tamoxifen was added to the collagen lattices. Lattice diameters were measured at intervals to assess the influence of tamoxifen on the lattice contraction. The reversibility of the inhibitory effect of tamoxifen on lattice contraction was investigated by 'washing out the tamoxifen' at different time-points. To visualise changes in the morphology of fibroblasts MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide] was added to the lattices. Tamoxifen at 1 and 5 microM had no significant influence on lattice contraction but higher concentrations of 50 and 100 microM completely inhibited contraction. At intermediate concentrations from 10 to 20 microM the degree of lattice contraction was dose-dependent. The reversibility of the inhibition was both dose- and time-dependent. Both the inhibition of contraction and the reversibility of inhibition appeared to correlate with changes in fibroblast morphology. The dose- and time-dependent inhibition of contraction by fibroblasts suggests that tamoxifen could be investigated as a novel potential therapeutic agent in treating abnormal dermal scarring.

Adult↗

The gene for severe combined immunodeficiency disease in Athabascan-speaking Native Americans is located on chromosome 10p.

Severe combined immunodeficiency disease (SCID) consists of a group of heterogeneous genetic disorders. The most severe phenotype, T-B- SCID, is inherited as an autosomal recessive trait and is characterized by a profound deficiency of both T cell and B cell immunity. There is a uniquely high frequency of T-B- SCID among Athabascan-speaking Native Americans (A-SCID). To localize the A-SCID gene, we conducted a genomewide search, using linkage analysis of approximately 300 microsatellite markers in 14 affected Athabascan-speaking Native American families. We obtained conclusive evidence for linkage of the A-SCID locus to markers on chromosome 10p. The maximum pairwise LOD scores 4.53 and 4.60 were obtained from two adjacent markers, D10S191 and D10S1653, respectively, at a recombination fraction of straight theta=.00. Recombination events placed the gene in an interval of approximately 6.5 cM flanked by D10S1664 and D10S674. Multipoint analysis positioned the gene for the A-SCID phenotype between D10S191 and D10S1653, with a peak LOD score of 5.10 at D10S191. Strong linkage disequilibrium was found in five linked markers spanning approximately 6.5 cM in the candidate region, suggesting a founder effect with an ancestral mutation that occurred sometime before 1300 A.D.

Alleles↗

Sciatic nerve blockade in infant, adolescent, and adult rats: a comparison of ropivacaine with bupivacaine.

BACKGROUND: Ropivacaine is a newly introduced local anesthetic. No data are available regarding its safety, efficacy, or sensory-selectivity in children. The sciatic block duration and systemic toxicity of bupivacaine and ropivacaine were compared among infant, adolescent, and adult rats. METHODS: Infant, adolescent, and adult rats received blocks with ropivacaine or bupivacaine. Nociceptive, proprioceptive, and motor blockade were assessed. Systemic effects (contralateral leg analgesia, seizures, respiratory distress, apnea) were quantified. Plasma local anesthetic concentrations were measured at terminal apnea. RESULTS: Nerve blockade for a given absolute dose lasted longer in infants than in older rats for both drugs. Block duration from ropivacaine generally was the same as or slightly shorter than bupivacaine. There was no difference in sensory-selectivity between the drugs. Doses required to induce all systemic toxicity indices were inversely related to age (e.g., the lethal dose in 50% of animals [LD50] of ropivacaine in infants is 155 mg/kg; in adults it is 54 mg/kg). All indices of toxicity occurred at higher doses per kilogram for ropivacaine than bupivacaine, at all ages (e.g., the LD50 of bupivacaine in infants is 92 mg/kg; in adults it is 30 mg/kg). Plasma concentrations at terminal apnea were higher for ropivacaine than for bupivacaine at all ages, and were higher in infants than in older rats. CONCLUSIONS: Ropivacaine resembles bupivacaine in its local anesthetic effects but has a greater margin of safety. For a given absolute dose, sciatic blockade in infant rats lasts longer than in adolescents or adults. Although the doses (in milligrams per kilogram) causing toxicity were much higher in infants than in adults, this probably does not correspond to a wider therapeutic index.

Aging↗

LMP-1, a LIM-domain protein, mediates BMP-6 effects on bone formation.

Glucocorticoids can promote osteoblast differentiation from fetal calvarial cells and bone marrow stromal cells. We recently reported that glucocorticoid specifically induced bone morphogenetic protein-6 (BMP-6), a glycoprotein signaling molecule that is a multifunctional regulator of vertebrate development. In the present study, we used fetal rat secondary calvarial cultures to determine genes induced during early osteoblast differentiation as initiated by glucocorticoid treatment. Glucocorticoid, and subsequently BMP-6, was found to induce a novel rat intracellular protein, LIM mineralization protein-1 (LMP-1), that in turn resulted in synthesis of one or more soluble factors that could induce de novo bone formation. Blocking expression of LMP-1 using antisense oligonucleotide prevented osteoblast differentiation in vitro. Overexpression of LMP-1 using a mammalian expression vector was sufficient to initiate de novo bone nodule formation in vitro and in sc implants in vivo. These data demonstrate that LMP-1 is an essential positive regulator of the osteoblast differentiation program as well as an important intermediate step in the BMP-6 signaling pathway.

Adaptor Proteins, Signal Transducing↗

Flow cytometric analysis for enterotoxin exposed on Clostridium perfringens spores.

Flow cytometric method (FCM) with fluorescent-labeled anti-CPE antibody was applied to develop a rapid, specific, and convenient method to detect enterotoxin (CPE) exposed on the surface of spores of Clostridium perfringens. The results obtained indicate that FCM can specifically detect CPE exposed on C. perfringens spores for a short time. Thus, FCM is found to be a rapid, specific, and convenient assay method for detection of CPE exposed on C. perfringens spores, suggesting that it will be hopefully useful to diagnose food poisoning caused by C. perfringens.

Animals↗

The caries-inhibiting effect of a fluoride drop program: a 3-year study on Chinese kindergarten children.

OBJECTIVE: To evaluate the caries-inhibiting effect of a fluoride drops program in two kindergartens in Chengdu, Sichuan Province, a fluoride-deficient area. METHODS: For 3 years, participating children ingested in school 0.25 mg fluoride daily, in the form of drops for 2 to 3-year-olds and 0.5 mg for children age 3 years and older. These systemic fluoride supplements were made available for over 180 days each year and they were distributed by teachers who maintained attendance records. Annual examinations were conducted for 176 2-year-olds who had used the supplements in the kindergartens and 148 control children. After 3 years, 128 test and 112 control children remained in the study. RESULTS: The results demonstrated a marked reduction in dental caries in the control group: test children had 2.21 decayed, missing, or filled teeth (DMFT)-versus 4.32 in the control group, a reduction rate of 48.84%. The mean DMFT increments over the 3-year period were 1.76 and 3.92, respectively. Over a 1- to 3-year period of supplement use, the group provided with the fluoride drops had consistently lower caries prevalence than the control group. The differences were statistically significant. CONCLUSIONS: This treatment regimen demonstrated an effective caries-inhibiting effect.

Cariostatic Agents↗

[The inhibitory effect of antisense phosphorothioate c-myc oligodeoxynucleotide on intimal hyperplasia in rat abdominal aortae after injury with a balloon catheter].

OBJECTIVE: To evaluate the effect of Antisense phosphorothioate c-myc oligodeoxynucleotide (ODN) on intimal hyperplasia in rat abdominal aortae induced by endothenial-denuded injury with a balloon catheter. METHODS: Antisense c-myc ODN was applied to the adventitia of injured abdominal aortae in rat introduced by pluronic gel releasing system and lipofectin delivery system. The animals were feeded with routine diet. Three weeks after intervention, the animals were killed and defined segments of arteries were sectioned and the histological sections were stained with elastic fiber staining. The cross-section of the artery was examined microscopically and the image was digitalized by image analysis system. The intima/media(I/M) area and I/M thickness ratios were calculated and analyzed statistically among groups. RESULTS: The intimal hyperplasia in antisense c-myc ODN-treated rats was inhibited significantly, demonstrated by microscopically and I/M area and thichness ratios, as compared with that treated with sense c-myc ODN and mismatch c-myc ODN. The larger dose of antisense c-myc ODN, the more obvious the suppression of intimal hyperplasia. CONCLUSION: The results suggest antisense c-myc ODN significantly suppressed the intimal hyperplasia in injured rat aortae in a sequence-specific fashion and dose-dependent manner. The investigation provides the basis for the early clinical trials assessing the therapeutic potential of antisense c-myc approach for the prevention of restenosis after angioplasty.

Angioplasty, Balloon↗

Long-term efficacy of recombinant interferon alpha 2a in the treatment of chronic hepatitis C: a randomized prospective study comparing two dose schedules in Chinese patients.

OBJECTIVE: To compare the long-term efficacy of a dose of 3 million units (MU) of r-IFN alpha 2a (IFN-alpha 2a) three times a week (t.i.w.) for 6 months with a starting dose 6 MU for 3 months and subsequent reduction to 3 MU t.i.w for further 3 months. METHODS: Sixty-eight serological and histological chronic hepatitis C patients with elevated serum alanine aminotransferase (ALT) were enrolled and randomized into two groups. Sixty-three patients were completed with full course of treatment. Five patients were withdrawn from trial (2 due to personal reasons and 3 due to adverse drug reactions during treatment). Thirty patients received 6 MU IFN-alpha 2a t.i.w., 3 months followed by 3 MU t.i.w. for another 3 months (Group A). Thirty-three patients received 3 MU IFN-alpha 2a t.i.w. for 6 months (Group B). RESULTS: The sex, age, baseline serum bilirubin, ALT and aspartate aminotransferase (AST) levels were matched in both groups. At the end of the 6th month, the complete and partial response rates in Group A were 60.0% and 16.7% respectively, and the clearance of serum HCV-RNA was 53.3%. In Group B, the complete and partial response rates were 72.7% and 6.1% respectively, and the clearance of HCV-RNA was 61.3%. The patients were followed up for 6, 12, and 18 months after stopping treatment. In Group A, the rates of complete normalization of ALT and clearance of serum HCV-RNA at 24 months were 50.0% and 60.0% respectively. In Group B, the rates of normalization of ALT and clearance of HCV-RNA at 24 months were 54.4% and 41.9% respectively. The efficacy between the two groups showed no statistically significant difference. The response rates of treatment were similar to those in the patients with HCV genotype 1b and 2a. Six patients (10.8% of the study population) developed neutralization antibodies to IFN-alpha 2a during treatment, and four of them were responded to the treatment. Adverse drug reactions (ADR), were common, but most of them were tolerable, and the incidence of ADR was in both groups, but the severity was higher in Group A. CONCLUSIONS: IFN-alpha 2a is effective in the treatment of Chinese patients with chronic hepatitis C. The sustained response rates and adverse drug reactions among two dose schedule groups are similar.

Adolescent↗

[Analysis of chemical components from Pheretima].

The total fat, total nitrogens, free amino acids, inorganic elements of Pheretima have been determined. It will provide scientific evidence for the establishment of quality standards of pheretima.

Amino Acids↗

Sonic hedgehog participates in craniofacial morphogenesis and is down-regulated by teratogenic doses of retinoic acid.

The face is one of the most intricately patterned structures in human and yet little is known of the mechanisms by which the tissues are instructed to grow, fuse, and differentiate. We undertook a study to determine if the craniofacial primordia used the same molecular cues that mediate growth and patterning in other embryonic tissues such as the neural tube and the limb. Here we provide evidence for the presence of organizer-like tissues in the craniofacial primordia. These candidate organizers express the polarizing signal sonic hedghog (shh) and its putative receptor, patched, as well as fibroblast growth factor 8 and bone morphogeneic protein 2. Shh-expressing epithelial grafts functioned as organizing tissues in a limb bud assay system, where they evoked duplications of the digit pattern. High doses of retinoic acid, which are known to truncate the growth of the frontonasal and maxillary processes and thus produce bilateral clefting of the lip and palate, inhibited the expression of shh and patched but not fgf8, in the craniofacial primordia, and abolished polarizing activity of these tissues. From these studies we conclude that the embryonic face contains signaling centers in the epithelium that participate in craniofacial growth and patterning. In addition, we discuss a novel mechanism whereby retinoids can exert a teratogenic effect on craniofacial morphogenesis independent of its effects on Hox gene expression or neural crest cell migration.

Animals↗

Catalytic properties and sensitivity to tentoxin of Chlamydomonas reinhardtii ATP synthases changed in codon 83 of atpB by site-directed mutagenesis.

The participation of the amino acid beta83 in determining the sensitivity of chloroplast ATP synthases to tentoxin was reported previously. We have changed codon 83 of the Chlamydomonas reinhardtii atpB gene by site-directed mutagenesis to further examine the role of this amino acid in the response of the ATP synthase to tentoxin and in the mechanism of ATP synthesis and hydrolysis. Amino acid beta83 was changed from Glu to Asp (betaE83D) and to Lys (betaE83K), and the highly conserved tetrapeptide betaT82-E83-G84-L85 (DeltaTEGL) was deleted. Mutant strains were produced by particle gun transformation of atpB deletion mutants cw15DeltaatpB and FUD50 with the mutated atpB genes. The transformants containing the betaE83D and betaE83K mutant genes grew well photoautotrophically. The DeltaTEGL transformant did not grow photoautotrophically, and no CF1 subunits were detected by immunostaining of Western blots using CF1 specific antibodies. The rates of ATP synthesis at clamped DeltapH with thylakoids isolated from cw15 and the two mutants, betaE83D and betaE83K, were similar. However, only the phosphorylation activity of the mutant betaE83D was inhibited by tentoxin with 50% inhibition attained at 4 microM. These results confirm that amino acid beta83 is critical in determining the response of ATP synthase to tentoxin. The rates of the latent Mg-ATPase activity of the CF1s isolated from cw15, betaE83D, and betaE83K were similar and could be enhanced by heat, alcohols, and octylglucoside. As in the case of the membrane-bound enzyme, only CF1 from the betaE83D mutant was sensitive to tentoxin. A lower alcohol concentration was required for optimal stimulation of the ATPase of the betaE83K-CF1 than that of CF1 from the other two strains. Moreover, the optimal activity of the betaE83K-CF1 was also lower. These results suggest that introduction of an amino acid with a positively charged side chain in position 83 in the "crown" domain affects the active conformation of the CF1-ATPase.

ATP Synthetase Complexes↗

[A new application of balloon catheter in TAE].

We report a new embolization method with cobra catheter and balloon catheter in TAE for aneurysms and arterioportal fistula. Embolization for one aneurysm and one arterioportal fistula was performed using a cobra catheter, and the target vessel was temporarily blocked using a balloon catheter during the intervention. 2 cases of aneurysms and arterioportal fistula were treated successfully without coils reflux. Application of both cobra catheter with balloon catheter in TAE is effective without complication.

Adult↗

Development of vicarious trial-and-error behavior in odor discrimination learning in the rat: relation to hippocampal function?

Previous work from our laboratory has suggested that hippocampal electrolytic lesions result in a deficit in simultaneous, black-white discrimination learning and reduce the frequency of vicarious trial-and-error (VTE) at a choice-point. VTE is a term Tolman used to describe the rat's conflict-like behavior, moving its head from one stimulus to the other at a choice point, and has been proposed as a major nonspatial feature of hippocampal function in both visual and olfactory discrimination learning. Simultaneous odor discrimination and VTE behavior were examined at three different ages. The results were that 16-day-old pups made fewer VTEs and learned much more slowly than 30- and 60-day-olds, a finding in accord with levels of hippocampal maturity in the rat.

Aging↗

Neurologic evaluation of infant and adult rats before and after sciatic nerve blockade.

BACKGROUND: Only limited data exist comparing differences in sensory function and responses to neural blockade in infant and adult rats. Therefore, the authors sought (1) to compare baseline thermal, proprioceptive, and postural responses in infant, adolescent, and adult rats; and (2) to compare the effects of sciatic nerve blockade on thermal, proprioceptive, and postural responses in infant, adolescent, and adult rats. METHODS: Infant, adolescent, and adult rats were evaluated for proprioceptive, thermal, and mechanical nociceptive and motor function before and after sciatic blockade using a detailed neurologic examination. RESULTS: Mechanical and thermal nociception were present in all rats, starting from age 1 day. The withdrawal reflex latency to pinch was rapid at all ages, whereas that reaction to thermal stimulus depended on both age and temperature. In contrast, the tactile placing response and hopping response were absent at birth and developed completely during the first 10 days of life. The extensor postural thrust was absent in the first 2 weeks of life and developed variably during the first 50 days of life. Sciatic blockade duration is shorter in infant rats than in adult rats receiving the same dose per kilogram. A brief halothane general anesthetic at the time of sciatic injection in infant or adult rats does not alter the duration of blockade. CONCLUSIONS: Infant rats show increased sensitivity to noxious thermal stimuli and similar response to deep mechanical stimuli compared with adult rats. Their proprioceptive and motor responses develop during the first 2 weeks of life. When doses are scaled by body weight, block duration is shorter in infant than in adult rats.

Age Factors↗

[Cultivation of intra-pulmonary arteriolar smooth muscle cell from rabbit].

By perfusion with trypsin at low concentration, the intra -pulmonary arterioles were separated carefully and cut into fine tissue pieces. These pieces were then washed with culture medium and used for culture of smooth muscle cells by method of adhesion to wall. Cells cultured were typical smooth muscle cells under light microscope, electron microscope and immunohistochemical test. The method is simple and convenient. It is also applicable to culture of vascular smooth muscle cells from other organs and provides ideal materials for vascular physiopathologic studies.

Animals↗