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Biomedical subjects

S Luo

Publications and source records attributed to S Luo.

At least 127 records · Page 7Linked to original sources

Dopaminergic neurotoxin administration to the area of the suprachiasmatic nuclei induces insulin resistance.

Dopaminergic neuron neurotoxin (6-hydroxydopamine; 6-OHDA) administration directed to the hypothalamic area of the mammalian pacemaker, the suprachiasmatic nuclei (SCN), was carried out on lean, glucose tolerant hamsters to investigate the possibility that dopaminergic input to the vicinity of the SCN is necessary to maintain this metabolic condition. Glucose tolerance tests (GTT, 3 g glucose/kg) were performed 4 days prior to and 16 days after neurotoxin lesioning. 6-OHDA administration to the area of the SCN resulted in both a significant 58% increase in daily food consumption by the 16th day post-lesioning, and a 85% increase in weight gain 4 and 8 weeks after lesioning relative to controls. Such treatment also significantly increased the total areas under the GTT glucose and insulin curves by 48% and 400% respectively, compared with controls. These findings indicate that body weight gain, glucose intolerance and insulin resistance result from decreased dopaminergic input to the area of the SCN.

Analysis of Variance↗

Comparative effects of 28-day treatment with the new anti-estrogen EM-800 and tamoxifen on estrogen-sensitive parameters in intact mice.

Following 28 days of oral administration, in intact mice, the novel non-steroidal anti-estrogen EM-800 was at least 30-fold more potent than tamoxifen in inhibiting uterine weight. Moreover, the maximal inhibitory effect achieved with tamoxifen on uterine weight was only 40% that with EM-800. The pure anti-estrogenic activity of EM-800 on the hypothalamo-pituitary-gonadal axis is illustrated by the increase in ovarian weight, while tamoxifen, due to its estrogenic activity, decreased ovarian weight. EM-800 is 10- to 30-fold more potent than tamoxifen in inhibiting uterine and vaginal estrogen receptors. Since 17beta-hydroxysteroid dehydrogenase (17beta-HSD) is the key enzyme in estradiol formation, the potent inhibitory effect of EM-800 on uterine 17beta-HSD could play an additional role by decreasing the availability of estradiol in the uterine tissue, while tamoxifen, on the contrary, stimulates activity of the enzyme. The atrophic changes in both the endometrial and myometrial layers achieved with EM-800 almost reached those observed 28 days after ovariectomy. EM-800 also resulted in a marked decrease in the number of ovarian developing follicles and corpora lutea, while the number of atretic follicles was increased. Tamoxifen treatment, on the other hand, produced an increase in both the number and crowding of the endometrial glands and a mild atrophy of the myometrial layer. Tamoxifen caused atrophic changes of the vaginal epithelium, especially at the highest doses, though the atrophy was much less pronounced than that following EM-800 treatment or ovariectomy. In addition to being at least 30-fold more potent than tamoxifen in inhibiting uterine weight, the novel anti-estrogen causes atrophy of the endometrium, stimulates the hypothalamo-pituitary-gonadal axis and inhibits uterine 17beta-HSD activity, while tamoxifen exerts opposite and estrogen-like effects on these parameters.

17-Hydroxysteroid Dehydrogenases↗

Daily dosing with flutamide or Casodex exerts maximal antiandrogenic activity.

OBJECTIVES: Because the large increase in luteinizing hormone secretion induced by flutamide in the intact rat is not found in men, we have used castrated rats and mice supplemented with androstenedione (4-dione) instead of intact animals to measure the activity of the pure antiandrogens flutamide and Casodex. METHODS: We first compared the effect of different schedules of administration of various doses of the two antiandrogens on prostate and seminal vesicle weights in the castrated rat and mice models. RESULTS: For both flutamide and Casodex, no consistent difference was found between the effects of once daily and thrice daily oral dosing in the rat. It was observed, however, that flutamide, especially at the high and therapeutically more effective doses, is about three times more potent than Casodex under both schedules of dosing. When flutamide was administered subcutaneously three times a day, twice a day, once a day, or once every second day in rats and mice, no difference was observed in the degree of inhibition achieved on prostate and seminal vesicle weights. CONCLUSIONS: The present data show that Casodex is about three times less potent than flutamide on the well-recognized parameters of androgen responsiveness in the rat, namely prostate and seminal vesicle weights. Another finding is that once daily dosing with flutamide exhibits an effectiveness comparable to thrice daily dosing; such data may have potential significance in facilitating compliance by administration of flutamide once daily instead of the current thrice daily schedule in men. Moreover, these data, if obtained in a reliable in vivo model, should be helpful in determining the choice of an appropriate dose of Casodex for the treatment of prostate cancer.

Androgen Antagonists↗

Immunoglobulin heavy chain junctional diversity in young and aged humans.

The causes of observed deficiencies to the humoral immune response in aged humans are unknown. Since a major source of antibody diversity is generated at the VH-D-JH junctional regions of the immunoglobulin heavy chain, we determined whether differences in junctional diversity are manifested with aging. We compared the CDR3 regions of IgM heavy chain transcripts isolated from young adult and aged humans. A PCR assay that measures CDR3 length in the majority of mu-heavy chains showed the same average size and normal range of CDR3 length in aged individuals as observed in young adults. To characterize the features of junctional diversity of aged adults in more detail, we determined the CDR3 sequences of a subset of the mu-heavy chain repertoire that utilizes members of the VH 5 family. In general CDR3 length, D family usage, and JH gene usage were similar in aged compared to young adults. Thus, in contrast to dramatic changes in heavy chain junctional diversity associated with fetal to adult development, no major differences were found between young and aged adults. Since the CDR3 repertoire generated in aged individuals appears to be as diverse as that observed in younger adults, the decline in humoral immunocompetence with aging cannot be attributed to a restriction in heavy chain junctional diversification processes.

Adult↗

Analysis of the host-specific haemagglutination of influenza A(H1N1) viruses isolated in the 1995/6 season.

Two phenotypes of human influenza A(H1N1) virus are currently circulating in Japan. One (group 1) agglutinates both chicken and goose red blood cells (CRBC and GRBC), the other (group 2) agglutinates GRBC but not CRBC. In the 1995/6 season, group 2 viruses accounted for 70% of the H1N1 viruses isolated in MDCK cells. The 1995/6 viruses were located on two branches of the genetic tree. One branch contained both group 1 and group 2 viruses and the other branch contained only group 2 viruses. Group 2 viruses had aspartic acid at residue 225 in the haemagglutinin (HA) protein, the key amino acid residue for group 2 phenotype. The HA protein of group 1 viruses had a change from aspartic acid to asparagine at residue 225 and the expressed HA protein of these viruses adsorbed CRBC. Serial passage of group 2 viruses in MDCK cells or embryonated chicken eggs caused these viruses to gain the ability to agglutinate CRBC. MDCK-adapted viruses had the same amino acid sequences of HA polypeptide as the original ones, but egg-adapted viruses had changed amino acid sequences. The expressed HA protein from one egg-adapted virus that originally belonged to group 2 adsorbed CRBC.

Amino Acid Sequence↗

Combined effects of dehydroepiandrosterone and EM-800 on bone mass, serum lipids, and the development of dimethylbenz(A)anthracene-induced mammary carcinoma in the rat.

Although treatment with dehydroepiandrosterone (DHEA) and the antiestrogen EM-800 alone decreased dimethylbenz(A)anthracene (DMBA)-induced mammary tumor incidence from 95% to 57% and 38%, respectively, approximately 9 months after DMBA administration, only two tumors developed in the group of animals that received the combination of DHEA and EM-800, and these two tumors disappeared before the end of the experiment (P < 0.01 vs. DHEA or EM-800 alone). Average tumor number per tumor-bearing animal as well as average tumor area per tumor-bearing animal were further decreased in animals that received the combination therapy compared with the effect of each treatment alone (P < 0.01). DHEA induced 6.9% (P < 0.01), 10.6% (P < 0.05), and 8.2% (P < 0.01) increases in bone mineral density of total skeleton, lumbar spine, and femur, respectively. The addition of EM-800 to DHEA did not affect the enhancing effect of DHEA on bone mass. The combination of the two drugs had important inhibitory effects on the urinary excretion of calcium and phosphorus as well as on the urinary hydroxyproline/creatinine ratio. Serum total alkaline phosphatase was stimulated by DHEA. Treatment with EM-800 decreased both serum triglyceride and cholesterol levels, whereas DHEA had an inhibitory effect on serum triglycerides. Although treatment with EM-800 caused a marked atrophy of the mammary gland, DHEA alone reduced lobular hyperplasia seen in aged intact rats while causing an androgen-specific stimulation of the same structures in animals already receiving the antiestrogen EM-800. The combination of DHEA and EM-800 lowered ovarian weight by 24% (P < 0.01) and decreased serum estradiol concentrations to intact control levels, whereas each compound alone had no effect on ovarian weight and stimulated serum estradiol levels by 45% (P < 0.05) and 46% (P < 0.05), respectively. Treatment with EM-800 caused a marked inhibition of uterine and vaginal weight. The present data show the additive inhibitory effects of DHEA and EM-800 on the development of DMBA-induced mammary carcinoma in the rat, thus suggesting the potential benefits of such a combination for the prevention of breast cancer in women while preserving or even increasing bone mass and maintaining a favorable lipid profile.

9,10-Dimethyl-1,2-benzanthracene↗

Morphological changes induced by 6-month treatment of intact and ovariectomized mice with tamoxifen and the pure antiestrogen EM-800.

The present study compares the effects of tamoxifen and EM-800, both administered at the oral daily dose of 100 microg for 6 months, on the uterus, vagina, and mammary gland in the mouse at histopathological examination. Treatment of intact animals with EM-800 resulted in uterine and vaginal atrophy even greater than that achieved after ovariectomy, while the developmental growth of the mammary gland was completely blocked and serum LH was increased. In ovariectomized animals, treatment with EM-800 decreased uterine and vaginal wt below the values observed in control ovariectomized mice while no significant change was observed on serum LH, thus indicating the lack of estrogenic activity of EM-800. Tamoxifen, on the other hand, showed a stimulatory estrogenic-like action on the mouse uterus in both intact and ovariectomized animals, thus resulting in moderate to severe endometrial hyperplasia. These morphological changes were accompanied by a marked stimulation of both the estrogenic and androgenic 17beta-hydroxysteroid dehydrogenase as well as 5alpha-reductase uterine activities. The histological atrophic changes observed in the vagina after tamoxifen treatment were less pronounced than those seen after treatment with EM-800. The agonistic estrogen-like action of tamoxifen was also illustrated by the suppression of serum LH levels in ovariectomized animals. A marked stimulation of the ovarian stroma, accompanied by a significant reduction in folliculogenic activity, was observed after EM-800 or tamoxifen administration, although the interstitial ovarian hyperplasia was more pronounced after EM-800 treatment. While both antiestrogens blocked the developmental growth of the mammary gland, EM-800 showed more potent antiestrogenic activity than tamoxifen. The highly potent and specific antiestrogenic activity of EM-800 suggests that this compound could improve the therapy of breast cancer while avoiding the undesirable stimulation of the endometrium.

17-Hydroxysteroid Dehydrogenases↗

Effect of dehydroepiandrosterone on bone mass, serum lipids, and dimethylbenz(a)anthracene-induced mammary carcinoma in the rat.

The present study investigated the effect of dehydroepiandrosterone (DHEA) on bone mass and serum lipids in the rat with dimethylbenz(a)anthracene (DMBA)-induced mammary carcinoma. The animals received DHEA once daily, percutaneously, at the dose of 5, 10, or 20 mg for 9 months following a single dose of 20 mg DMBA at 50-52 days of age. Bone mineral content (BMC) and bone mineral density (BMD) of total skeleton, lumbar spine, and femur were measured by dual energy x-ray absorptiometry. A 9-month treatment with DHEA increased BMC and BMD of total skeleton by 14.2% to 14.5% (all P < 0.01) and 6.7% to 8.3% (all P < 0.01), respectively. Similarly, femoral BMC and BMD were stimulated by 13.6% to 14.7% (all P < 0.05) and by 8.1% to 9.5% (all P < 0.01), respectively. In addition, BMD of lumbar spine was increased by 10.4% to 10.8% (all P < 0.05), whereas the 9.4% to 11.1% increment in BMC of lumbar spine was not statistically significant. Treatment with DHEA led to 26% (NS), 60% (P < 0.01), and 62% (P < 0.01) decreases in serum triglyceride levels at the same doses. On the other hand, no significant change in serum cholesterol concentrations was observed. Two hundred and seventy-nine days after DMBA administration, the incidence of mammary carcinoma had decreased from 95% in control animals to 73% (P < 0.05), 57% (P < 0.01), and 38% (P < 0.01) at the daily percutaneous doses of 5, 10, and 20 mg of DHEA, respectively. Moreover, the mean tumor number per tumor-bearing animal and the mean tumor area per tumor-bearing animal were also reduced by the same treatments. DHEA increased serum total alkaline phosphatase activity and decreased urinary calcium excretion, but had no effect on the urinary ratio of hydroxyproline to creatinine and urinary phosphorus excretion. These data show that DHEA exerts a stimulatory effect on bone mass and an inhibitory effect on serum triglycerides, as well as a preventive effect on the development of mammary carcinoma induced by DMBA in the rat. Such data suggest that while decreasing the risk of breast cancer, DHEA replacement therapy could also exert beneficial effects on the bone and lipid metabolism in women receiving DHEA replacement therapy.

9,10-Dimethyl-1,2-benzanthracene↗

[Clinical experience in the treatment of chronic radiation ulcer in 32 cases].

A retrospective study was carried out, aiming at a proper treatment to the chronic radiation ulcer that is often difficult to deal with. Thirty-two cases of chronic radiation ulcer have been treated in the department since 1983. The cause, site, features and method of treatment were summarized. Thirty-one cases were cured, 26 cases healed by the first intention, 5 cases healed by the second intention. One died. It is emphasized that more knowledge should be gained for understanding and treatment of the chronic radiation ulcer. Different methods of debridement and repair should be performed according to the site, depth and pathologic features of the ulcer. To improve local circulation, an island flap is the first choice of treatment.

Breast Neoplasms↗

[A study on the changes of the estrogen level in the condylar cartilages in young growing rats after functional mandibular protrusion].

Fifty female SD rats of 4-week-old were selected, divided equally and randomly into experimental and control groups. Simulated functional appliances were used to guide the mandibles of the rats forwards. The animals were sacrificed after 3 days, 1 week, 2 weeks, 3 weeks and 4 weeks. The method of radioimmunoassay (RIA) was performed to quantitively detect the level of estrogen in the condylar cartilages. The results showed: 1. High levels of estrogen were detected in the condylar cartilages during their actively proliferative period. When they differentiated gradually, the levels of estrogen decreased. 2. The amount of estrogen was increased significantly after functional mandibular protrusion, especially during the period of the active proliferation of the condylar cartilages. It is suggested that estrogen has a close relationship with the hyperplasia and hypertrophy of the condylar chondrocytes and the increment of the levels of estrogen in the condylar cartilages will further promote the proliferation and functional adaptive remodelling of the condylar cartilages.

Animals↗

[Histologic and SEM studies on aging changes of temporomandibular articular disc in young growing rats].

The normal aging changes of the temporomandibular articular discs in young growing SD rats were studied with histologic and scanning electron microscope methods. The results showed that the active remodeling growth was found in the discs of the rats from 3 to 9 weeks, which characterized as the changes from the young cellular connective tissues to fiberous cartilage gradually, these changes were consistent and adaptable with the growth of the condyle. The wave-like structures on the superior surface of discs of the rats from 5 to 8 weeks were varied morphologically in different bands and ages.

Age Factors↗

[Histologic and histochemical studies on the temporomandibular articular disc in young growing rats after functional mandibular advancements].

The purpose of these studies was to detect the patterns of the changes in the site of temporomandibular articular disc in the young growing SD rats after the functional protrusive appliance inserted with histologic and histochemical methods. The results showed that collagen fibres were dense, roughly paralleled linked especially anterioposteriorly after the mandible protruded functionally, chondrocytes and gycosaminoglycans contents increased apparently in the posterior band of the discs. The adaptive remodeling of the discs might be the results of the pressure of the condyle on the discs and the lateral pterygoid muscle to it. The remodeling growth of the discs were coordinate and adaptive with the proliferative changes of the condylar cartilage after the mandible protruded functionally. No pathological changes were found in the rat articular discs.

Animals↗

[Immunohistochemical study on the temporomandibular articular disc in young growing rats after functional mandibular advancements].

In the present experiment the type I collagen of discs was investigated with immunohistochemistry in the young growing SD rats after the mandible protruded functionally. The experimental evidence showed that the immunohistochemical staining reactions accentuated with age changed in control group discs, and the immunohistochemical staining reactions in experimental group were intenser than in control group. It indicated that the discs synthesized higher contents of type I collagen after the disc accepted more functional stimuli in the experimental group.

Age Factors↗

[A study of craniofacial type of skeletal anterior crossbite in juveniles].

Lateral skull radiographs of 69 subjects with Class III malocclusion, 35 boys, 34 girls, aged 10-13 years old, were compared to a control group of similar mean age based on hierarchical cluster analysis. Cranial base, maxilla, mandible, relationships of sagital and vertical, teeth and soft tissue were evaluated together. Four subgroups of malocclusion were identified and described at the first time. The subgroup of maxillary deficiency, mandibular prognathism due to moved forward joint and lower anterior face height was the most common type. The results indicated that it should be evaluated a lot of indices together on cephalometric analysis.

Adolescent↗

[Orthodontic treatment for the surgical correction of mandibular skeletal retrognathism].

The purpose of this paper is to discuss the combining orthodontic treatment that is based on seventeen consecutive patients of severe mandibular skeletal retrognathism who have been treated by orthognathic surgery. Not only the presurgical preparation, but also the presurgical and postsurgical orthodontic treatment and the use of interocclusal splints were introduced. The goals of orthodontic treatment for patients with orthognathic surgery are (1) decompensating the teeth, expanding the upper dental arch, (2) aligning the teeth, (3) leveling the curve of Spee, (4) making the shape and width of upper and lower dental arch harmonious, (5) getting the occlusal equilibrium and fine occlusal contact. The author's experience indicates that: in order to get satisfactory results of esthetics and function, the combination of surgical and orthodontic treatment, the presurgical and postsurgical orthodontic treatment is absolutely necessary and important.

Adolescent↗

[Determination of liensinine in plasma by high performance liquid chromatography].

A sensitive method of high performance liquid chromatography (HPLC) for determination of liensinine in plasma is reported. An Ultrasphere Si column, 250 mm x 4.6 mm i.d. with dichloromethaneisopropyl alcohol-diethylamine (75:25:0.2, V/V) as mobile phase at a flow-rate of 1.0 mL/min and UV-detector at 282 nm were used. Neferine was served as the internal standard. Liensinine in plasma was extracted with diethyl ether three times after adding ammonia-ammonium chloride buffer (pH 10). Liensinine was completely separated from nefrine. The retention times of liensinine and neferine were 8.5 and 5.0 minutes, respectively. The calibration line of liensinine was linear in the range of 0.0625-5.0 mg/L (r = 0.9996). The mean recovery was 93.6% with RSD of 1.9%. The precision of intra-day and inter-day for liensinine was in the range of 1.4%-4.1% and the detectable limit was 0.025 mg/L based on a signal-to-noise ratio of 3. The results showed that the method was simple and sensitive.

Chromatography, High Pressure Liquid↗

[Clinical features of hemangioblastomas of the central nervous system].

OBJECTIVE: To study the clinical features of hemangioblastomas of the central nervous system (CNS). METHODS: 174 patients with hemangioblastomas of CNS were reviewed from 1982 to 1995. All patients were verified pathologically. RESULTS: The tumors occurred mainly in patients between 21 and 40 years of age, and more often in men than in women. Most tumors were in the posterior fossa. CT scan of 119 patients showed that 95 hemangioblastomas appeared as cysts. Magnetic resonance imaging (MRI) for 47 patients showed that 32 had cysts. 49 patients were examined with angiography or DSA. 164 tumor mural nodules and solid masses were completely resected. The subtotal removal of others was performed. These patients received radiotherapy. CONCLUSION: Enhanced MRI is the examination of choice for preoperative evaluation of cystic hemangioblastomas. Angiography or DSA is necessary in the diagnosis of bigger solid masses. The findings suggest that patients' age and degrees of section could affect the recurrence of hemangioblastoma.

Adolescent↗